Aptamer-engineered (nano)materials for theranostic applications

Abstract

A diverse array of organic and inorganic materials, including nanomaterials, has been extensively employed in multifunctional biomedical applications. These applications encompass drug/gene delivery, tissue engineering, biosensors, photodynamic and photothermal therapy, and combinatorial sciences. Surface and bulk engineering of these materials, by incorporating biomolecules and aptamers, offers several advantages such as decreased cytotoxicity, improved stability, enhanced selectivity/sensitivity toward specific targets, and expanded multifunctional capabilities. In this comprehensive review, we specifically focus on aptamer-modified engineered materials for diverse biomedical applications. We delve into their mechanisms, advantages, and challenges, and provide an in-depth analysis of relevant literature references. This critical evaluation aims to enhance the scientific community's understanding of this field and inspire new ideas for future research endeavors.

Full text

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Theranostics
2023; 13(15): 5183-5206. doi: 10.7150/thno.85419
Review
Aptamer-engineered (nano)materials for theranostic
applications
Navid Rabiee1,2, Suxiang Chen1,2, Sepideh Ahmadi3,4, Rakesh N. Veedu1,2
1. Centre for Molecular Medicine and Innovative Therapeutics, Health Futures Institute, Murdoch University, Perth, WA 6150, Australia.
2. Perron Institute for Neurological and Translational Science, Perth, WA 6009, Australia.
3. Student Research Committee, Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical
Sciences, Tehran, Iran.
4. Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
 Corresponding authors: Dr. Navid Rabiee (navid.rabiee@murdoch.edu.au); Assoc. Prof. Rakesh N. Veedu (r.veedu@murdoch.edu.au).
© The author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/).
See http://ivyspring.com/terms for full terms and conditions.
Received: 2023.04.19; Accepted: 2023.08.09; Published: 2023.09.25
Abstract
A diverse array of organic and inorganic materials, including nanomaterials, has been extensively
employed in multifunctional biomedical applications. These applications encompass drug/gene delivery,
tissue engineering, biosensors, photodynamic and photothermal therapy, and combinatorial sciences.
Surface and bulk engineering of these materials, by incorporating biomolecules and aptamers, offers
several advantages such as decreased cytotoxicity, improved stability, enhanced selectivity/sensitivity
toward specific targets, and expanded multifunctional capabilities. In this comprehensive review, we
specifically focus on aptamer-modified engineered materials for diverse biomedical applications. We
delve into their mechanisms, advantages, and challenges, and provide an in-depth analysis of relevant
literature references. This critical evaluation aims to enhance the scientific community's understanding of
this field and inspire new ideas for future research endeavors.
Keywords: nanomaterials; aptamer; aptamer modified materials; biosensors; biomedical engineering
Introduction
Nanomaterials refer to materials composed of
small particles with sizes ranging from 1 to 100
nanometers. These materials possess unique
properties that make them highly valuable in various
applications, including medicine [1-3]. For instance,
lanthanide-doped upconversion nanoparticles
(UCNPs) exhibit nonlinear light transformation,
exceptional stability, and resistance to photo-
bleaching. Magnetic nanomaterials demonstrate
superparamagnetic characteristics, while carbon
nanomaterials exhibit a broad range of absorbance
[4-6]. Metal-organic frameworks (MOFs) exhibit desi-
rable features such as tunable porosity, appropriate
size, and engineered morphology, making them
well-suited for biomedical applications [7, 8].
Liposomes, consisting of a lipid layer and a core for
encapsulating drugs, are among the first nano-scale
materials for drug delivery. By modifying the lipid
layer, liposomes can fulfill multiple functions,
enabling effective drug delivery [9]. Polymer-based
nanoparticles offer specific structures tailored for
various applications, including gene/drug delivery
[10, 11]. One commonly used polymer nanoparticle is
polylactic-co-glycolic acid (PLGA), which demons-
trates excellent compatibility and degradation
properties, making it widely utilized as a drug carrier
for cancer therapy. However, PLGA does have
limitations in terms of stability. Dendrimers, on the
other hand, are versatile and biocompatible
macromolecules with functional groups on their
surface that enhance their ability to deliver
therapeutic drugs [12, 13].
Recently, there has been a shift in (nano)material
applications from a laboratory setting to a cellular
level, with applications including imaging,
drug/gene delivery, and cancer therapy. However,
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many nanomaterials tend to accumulate non-specifi-
cally in tissues due to the enhanced permeability and
retention (EPR) effect and lack the capability to
selectively target specific regions of interest (ROI). As
a result, the potential toxicity of nanoparticles in
non-target tissues has limited their applications in
biological fields [14, 15]. To overcome these
limitations, various techniques have been used to
decorate nanomaterials with molecules to enhance
their selectivity.
Aptamers are short single-stranded (ss) RNA or
DNA molecules identified through the Systematic
Evolution of Ligands by EXponential enrichment
(SELEX) process (Scheme 1). The SELEX method
involves the selection of nucleic acid sequences
comprising variable regions of 30 to 60 nucleotides,
flanked by fixed regions of 15 to 30 nucleotides on
each end, to form the starting pool. These
oligonucleotides are incubated with the target
molecule, and the sequences that bind to the target are
isolated, purified, and amplified through polymerase
chain reaction (PCR). This iterative process is repeated
multiple times to refine and enrich the sequences that
demonstrate affinity for the target. For DNA
aptamers, the initial incubation requires ssDNA. To
achieve this, the 3' primer is biotinylated, and it is
separated from the complementary strand using
streptavidin beads. The purified DNA sequences from
each round are utilized for subsequent iterations. To
isolate RNA aptamers, a 5' primer containing a T7
RNA polymerase promoter is first annealed with a 3'
primer. Double-stranded (ds) DNA is then generated
through extension using the Klenow fragment or
multiple rounds of PCR. This dsDNA is transcribed
into ssRNA, which interacts with the target.
Subsequently, the 3' primer is annealed to the RNA in
the presence of a transcriptase enzyme to synthesize
complementary DNA (cDNA). This cDNA is then
amplified through PCR to generate dsDNA [16].
Aptamers can bind to an extensive range of
targets, including proteins, ions, and biomolecules
with great affinity [17, 18]. Aptamers offer numerous
advantages over antibodies. These benefits include
high reproducibility, low molecular weight, small
size, and absence of immunogenicity or toxicity [19,
20]. Aptamers, in particular, have become popular
due to their capacity of highly selective target
recognition [21-24]. The nature of nucleic acids also
makes aptamers useful in biological applications.
Aptamer sequence can be modified to allow tunable
recognition of targets. Aptamers have been explored
for use as sensing tools for drug monitoring and
disease diagnosis, and also for use in therapeutics
either through targeted delivery of therapeutic cargo
into cells or regulating protein function to influence
biological processes [25-27]. Although several
aptamer-based drugs are now in clinical testing, one,
Pegaptanib, is already on the market to treat
age-related macular degeneration (AMD). However,
natural nucleic acid aptamers can be degraded by
nucleases in complex environments, which restricts
their use. To address this issue, aptamers can be
conjugated to carriers to increase their resistance to
nucleases. Aptamers offer the advantage of being
easily modified with functional groups, allowing for
their attachment to nanomaterials and manipulation
upon target binding [28, 29]. By introducing an
antidote, the conformation of an aptamer can be
altered, resulting in release of the target. This
technology has been successfully utilized to control
anticoagulation levels in patients requiring
anticoagulation therapy. Aptamers can be chemically
synthesized, enabling convenient functional group
attachment at their ends [30]. It is worth noting that
many benefits that are attributed to aptamers, such as
their appropriate size and capacity for
functionalization with various groups, are shared by
other targeting molecules, including small antibodies
and biomolecules [31]. Consequently, careful
consideration should be given to selecting the most
suitable targeting biomolecule for a specific
application, considering scientific and practical
factors. Scientific considerations include factors like
charge, size, binding affinity, and ligand stability. In
the case of antibodies, it is also crucial to consider
their potential to trigger antibody-dependent
cell-mediated cytotoxicity [32, 33]. Aptamers have
further been incorporated into the development of
nanomaterials for drug delivery purposes within
biological environments [34-37].
One of the main challenges in using aptamers in
bioapplications is their relatively short serum
half-lives, which can limit their effectiveness.
Researchers have developed several strategies to
address this issue, including using aptamer conju-
gates and developing new SELEX techniques.
Aptamer conjugates are aptamers that are chemically
linked to a carrier molecule, which can increase their
stability and thereby extend their serum half-lives. In
fact, the molecular weight of aptamers (<20 kDa) is
lower than the renal filtration threshold (50 kDa),
causing a short half-life, which restricts their potential
use as therapeutic agents. (Nano)materials and
biomolecules can be developed for enhanced drug
loading, increased half-life in the body, and selective
distribution by modifying their composition, size, and
morphology [38]. PEGylation can reduce the
bottleneck in developing aptamers into therapeutics,
through extending their circulation half-life and
reducing nanoparticle aggregation [39, 40]. One study

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showed that Apt-paclitaxel (PTX)-NP exhibited a
much longer elimination half-life and slower
clearance rate than PTX-Apt [41]. PLGA/PEG
nanoparticles can protect aptamer from degradation
and increase circulation time of Apt-nanoparticles
(half-life of Apt-PTX-NP was 4h). Aptamer-
conjugated chitosan nanoparticles can considerably
increase the efficiency of traditional therapies,
decrease their side effects on normal tissues, and
overwhelm the enhanced EPR effect caused by the
nanomaterial. Besides, these conjugations help to
increase their half-life in bodily fluids via enhancing
the nuclease resistance of aptamers [42]. Another
study showed the stability and high half-life of
A3-APOHis during 28 h, which is higher than other
associated peptides. A3-APOHis was not observed in
the organs of mice injected with APOHis alone,
AuNP-AptHis significantly increased the cell
penetrating capability of A3-APOHis in mice [43].
Novel SELEX techniques, such as modified
SELEX (mod-SELEX) and circular SELEX (cSELEX),
have also been established to enhance the stability of
aptamers [44]. One of the most promising areas of
research in aptamer nanotechnology is drug delivery.
Aptamers can be designed to target cancer cells,
diseased tissue, or proteins, making them ideal
candidates for delivering therapeutic cargo to specific
locations in the body. Apart from its role in drug
delivery, aptamers can also be used to directly
regulate protein function, which can influence
vigorous biological procedures such as immune
stimulation pathways. As mentioned earlier, some
therapeutic aptamers are currently under clinical
investigation, and Pegaptanib was approved by the
US Food and Drug Administration (FDA) to treat
AMD. Furthermore, aptamers are used for imaging
and diagnosis. Aptamers can be labeled with various
imaging agents, such as fluorescence dyes or
radioisotopes, which can be used to visualize specific
targets in the body, thereby benefiting disease
progression monitoring and cancer therapy [45-47].
The Cell-SELEX process aims to recognize
aptamers that specifically bind to a particular cell
type. The Cell-SELEX method can be applied to
generate aptamers that are capable of targeting
nanoparticles to tissues of interest by identifying
unique molecular features of targeted cells. For
example, Cell-SELEX has been applied to isolate an
aptamer that targets glioblastoma, a type of brain
cancer [48]. Cell-SELEX has also been used to isolate
aptamers that prevent the reorganized throughout
transfection (RET) receptor tyrosine kinase, which is
involved in cancers. Aptamers selected using the
Cell-SELEX method may be capable of enhancing the
targeting of nanoparticle-aptamer conjugates to
targeted cells, as well as potentially improving the
intracellular delivery of nanoparticles. In fact, the
selection process can enrich the set of aptamers that
can escape endosomal degradation. While aptamers
that facilitate cytosolic delivery have the potential to
be used in conjunction with nanomaterials, their
function in this context would still need to be
validated and confirmed. Researchers are also
exploring approaches to deliver aptamers across the
cell membrane, which could lead to innovative
applications of nanotechnology. The Tan group used
Cell-SELEX to develop aptamer molecular probes for
identifying, analyzing, and isolating tumor cells. They
recognized a group of aptamers connecting to a T-cell
acute lymphoblastic leukemia cell line. These
aptamers, labeled with fluorescence dyes and
analyzed using flow cytometry, allowed the team to
identify target cells inside samples like bone-marrow
aspirates. They also confirmed that the aptamers were
internalized by leukemic T cells [49-51].
Although a number of review articles have been
published about aptamer-conjugated materials in
theranostic applications [52-54], the present work
provides a broad perspective on aptamer-conjugated
(nano)materials, including organic and inorganic
materials, and their different theranostic applications,
such as diagnosis, gene/drug delivery, and cancer
therapy. Finally, we provide an in-depth discussion
about the challenge of these aptamer-nanomaterial
systems along with casting a significant eye over the
issue.
Aptamer-assisted nanotechnology
Aptamers have many potential applications in
nanotechnology to treat diseases. They are
particularly useful in this context due to their small
size, allowing them to be used in drug delivery
devices without significantly increasing the device's
overall size and allowing for cell or tissue selectivity
[55]. Aptamers potentially work for a large range of
potential drug delivery due to their capability to
connect to various targets, such as hepatitis C virus
proteins, thrombin, HIV-1, and human thyroid-
stimulating hormone. Aptamers can be applied to
block antibodies that bind to the insulin receptor,
which could interfere with the treatment of insulin
resistance. Aptamers capable of binding to vascular
endothelial growth factor (VEGF) can play a
significant role in anti-angiogenesis. This aptamer has
received FDA approval to treat AMD. Aptamers can
act as inhibitors themselves without requiring related
toxins, but long-term data is required to measure their
toxicity when injected intravenously [56, 57].
Drug-loaded nanoparticles have shown
promising results in preclinical studies. Conjugating

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aptamers to nanoparticles can lead to targeting
specific cells with increased precision, thus improving
efficacy of therapeutics and specificity of diagnosis.
For example, the A10 aptamer has been conjugated
into nanoparticles and used to target the
prostate-specific membrane antigen (PSMA), a
transmembrane protein overexpressed in prostate
cancer. This platform was investigated in the lateral
tumor model of LNCaP prostate cancer, and the
effective reduction of tumor size was observed after
intratumoral injection [58]. Aptamer-toxin conjugates
can be used as a therapeutic agent. For example,
conjugating the A9 aptamer with Gelonin as a
ribosomal toxin caused 600-fold improved potential
in cell death in cells expressing PSMA and reduced
toxicity in non-targeted cells [59]. Aptamers have also
been applied to release anthracycline chemothera-
peutics and to create quantum dot–aptamer
conjugates that can identify cancer cells and
determine if a drug has been delivered. By fixing
aptamers on carbon nanotubes, the presence of
analytes can be detected, and they can be used to
create smart nanostructures to detect analytes [60-62].
Conjugation strategies
Nanomaterials could be modified with various
kinds of aptamers as ligands. These modifications are
attained by different methods, such as covalent bonds
and physical conjugation approaches which were
applied via a linker to preserve aptamer binding
activity. In nanomaterials, their surface allows the
anchoring of different aptamers. Besides, aptamers
have terminal functional groups with high flexibility.
Covalent and non-covalent strategies are the two most
common techniques.
Non-covalent strategies
In this type of strategy, electrostatic interactions,
hydrogen bonding interactions, π-π interactions, and
van der Waals interactions are involved in the
formation of bonds between aptamer and nanoma-
terials [63]. DNA bases can use π-π stacking and
hydrogen bonds to interact with graphene oxide (GO)
[64]. Based on these strategies, some effective
modifications are established, such as using
imidazolium ring groups to offer self-assembly
properties and biotin-avidin interactions [65, 66].
Direct self-assembly of DNA into nanostructures has
different applications. For example, conjugation of
aptamers on avidin-liposomes was performed
through avidin-biotin interaction, where an
anti-platelet-derived growth factor receptor aptamer
was connected to DOX-liposomes sensitized using
poly (NIPMAM-co-NIPAM) [67].
Scheme 1. Schematic illustration of the general process of Systematic Evolution of Ligands by EXponential enrichment (SELEX).

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Covalent strategies
Covalent strategies are more often applied in the
modification of nanomaterials, since they are more
stable than the non-covalent strategies. Therefore,
covalent interactions are broadly applied to the
synthesis of nanomaterials with various functional
groups [68]. Aptamers can be attached directly to the
surface of nanoparticles, although some scientists use
linkers to connect aptamers by covalent bonds. Thiol
is the linker for gold (Au) nanoparticles to connect a
biomolecule with the nanoparticles. Thiol maleimide
coupling chemistry is generally used for the
conjugation of thiolated (-SH) molecules to the surface
of nanomaterials in drug delivery systems [69].
Hydroxyl, Amine, and carboxylic acid are other
groups on the surface of nanomaterials. The aptamer
conjugation was attained through carbodiimide
chemistry, where the D-ɑ-tocopheryl polyethylene
glycol succinate (TPGS) polymer was treated with
succinic anhydride to attain carboxyl-modified
polymer, and an amine-modified AS1411 aptamer
was added to the EDC/NHS-activated TPGS
polymer. This platform showed greater cellular
uptake and major cytotoxicity [70]. However, these
moieties are solvent-exposed to react, and these
approaches for modification are not suitable. Some
illustrative studies are demonstrated as follows.
Amine moieties can be reacted with p-isothiocyanate
or N-hydroxy-succinimide esters for functionalization
[71]. Nanomaterials with hydroxyl groups can be
modified with carbonyldiimidazole to form a reactive
intermediate. Besides the epoxy groups can be used in
function with aptamers, which are applied for amine
groups-contained aptamers [72].
Aptamer-embedded DNA
(nano)materials
In addition to their role in transmitting genetic
information, DNA can be used as molecular building
blocks to form various types of (nano)materials with
manageable sizes, shapes, and functions based on
Watson-Crick hybridization, enabling the progress of
DNA nanotechnology. Aptamers can be integrated
into DNA (nano)materials, creating aptamer-
embedded DNA (nano)materials including DNA
nanostructures, DNA-based micelles/polymers, DNA
hydrogels, and DNA-functionalized liposomes. These
(nano)materials have shown great potential for
biomedical applications [73].
DNA nanostructures
DNA nanostructures are nanoscale structures
formed of DNA, which acts as a functional element. In
fact, they can act as scaffolds for the fabrication of
complex structures [74]. DNA nanostructures have
been widely applied for the management of biological
procedures, which is necessary in investigating the
molecular mechanism of biomedicine. DNA
nanostructures have several applications in
biosensing, treatment, and therapeutic agent delivery.
As a result, modified DNA structures with theranostic
moieties were applied for the targeting of different
immunological, cancer, and metabolic diseases [75,
76].
The unique capability of aptamers to identify
and connect to cancer cells makes them valuable
apparatuses for precise cancer treatment. This is
because aptamers can be combined into DNA
nanostructures through hydrogen bonding
interactions. This allows for specific cell recognition
and following applications. For instance, researchers
developed an aptamer-modified DNA structure,
"Nano-Claw", that is capable of investigating
cancerous cells and being utilized in targeted therapy
[77]. Peng and colleagues developed a 3D DNA
nanomachine that was designed for specific targeting
of biomarkers. The nanomachine was composed of a
DNA of triangular shape with prolonged toes on the
top and both sides of faces (Figure 1A). The toes on
the top face performed as reporters and were made up
of three strands: S, F, and R. On the bottom face, two
separate recognition toes performed as an "AND"
Boolean operator. As each edge of the triangle showed
a single-strand domain for hybridizing functional toes
(Figure 1B), a toes-loaded DNA nanomachine was
developed. The nanomachine was able to recognize
and bind to two types of membrane biomarkers that
were overexpressed on CCRF-CEM cells, and the
AND operator returned an accurate value, activating
the reporter toes via DNA displacement. The
nanomachine demonstrated improved molecular
recognition compared to other molecular paths based
on dsDNA and could accurately recognize specific
cell subtypes [78].
Researchers developed a DNA logic device that
activated aptamers via hybridization reaction to
precisely recognize specific cells from a large
population of similar cells [79]. Multiple aptamers
that target membrane receptors can be applied. A
toehold-based reaction occurs by simultaneously
binding several aptamers to cells, which enables the
detection and amplification of the signal from the
target cells. Also, these aptamer-decorated DNA
nanostructures can be used as smart biosensors to
measure intracellular biomolecules for cellular
interactions [80, 81]. Li and colleagues presented the
development of a DNA probe that is compatible,
efficient, and adaptable in its ability to use cell
connections. The probe's design incorporated the
structural rigidity of 3D pyramidal DNA. Compared

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to linear DNA probes, the pyramidal probes
demonstrated significantly enhanced stability for cell
membrane anchoring, with an approximately 100-fold
increase. Additionally, the pyramidal probes showed
a 2.5-fold increase in target accessibility between two
different kinds of cells. Using these probes allowed
the researchers to investigate the role that close
proximity plays in cell interactions, and they found
that it is crucial. Therefore, this approach enables
nanoplatforms to study cell membrane anchoring in
cell communication networks [81].
Scientists have used molecular engineering
techniques to create DNA nanostructures with
aptamers embedded in them to carry therapeutic
agents to specific cells or areas of the body. One
example of this is the use of aptamer-based nano
assemblies that can target certain types of exosomes
(tiny vesicles released by cells) while ignoring others,
allowing for the accurate delivery of DNA nano
assemblies to specific organelles (tiny structures
within cells) [82, 83]. In 2013, a group of researchers
led by Zhu created aptamer-tethered DNA nanotrains
(aptNTrs) to deliver doxorubicin (DOX) to specific
cells. These aptNTrs used aptamers to target the cells
[84]. aptNTrs were self-assembled from two DNA
commenced by aptamers, which act as locomotives
train toward tumors. sgc8 was internalized by target
CEM cells through endocytosis. aptNTrs worked as
carriers with a great payload capacity of drugs that
were transported to target cells and prompted
cytotoxicity. In fact, aptNTrs increased the maximum
-tolerated dose in nontarget cells. More recently, a
group of researchers led by Xue created a DNA
nanowire (NW) to target cancer cells for imaging and
therapy. This NW consisted of multiple binding DNA
helices assembled using two structural units, with
terminal-hidden aptamers on the surface that
recognize tumor cells. Aptamer-DOX DNA NWs can
enter the blood circulation through endocytosis of
cells in blood and are able to accumulate in target
tissues. The aptamer can bind to the membrane
protein tyrosine kinase-7 (PTK7) overexpressed by
cells and it can fold into a hairpin structure [85].
Another group of researchers, led by Ouyang,
developed a DNA nanoscale precision-guided missile
(D-PGM) for the targeted delivery of therapeutic
agents to target cells, to improve the effectiveness of
treatment. The D-PGM is formed with a DNA
structure for loading the therapeutic agents and a
control system to achieve a great payload. They used
aptamers bound to target cells as an "initiator" for the
guidance/control (GC) system of the D-PGM. The GC
system is based on an aptamer-based logic gate, and
the warhead (WH) is a DNA self-assembled 3D
structure containing a therapeutic agent called DOX.
When the D-PGM reaches the tumor tissue, the GC
system can be disassembled, allowing the D-PGM to
bind to and be taken up by target CEM cells,
providing a more efficient drug delivery system and
lowering toxicity to non-target cells. Li and
co-workers created a drug delivery system called
Apt-ND-ABP, consisting of a backbone made of
miR-21 and miR-150 and easily loaded with small
RNA molecules such as siRNA or miRNA [86, 87].
When the Apt-ND-ABP binds to A549 cells, it is taken
up into the cell's cytoplasm. It activates the release of
multiple antisense oligonucleotide, preventing the
function of specific miRNAs and the controlled death
of the target cells (apoptosis). Another group of
researchers, led by Ren, used a lock-and-key
technique to precisely deliver siRNA to specific cells.
They employed two DNA aptamers, sgc8c, and sgc4f,
that bind to the cell membrane of target CEM cells as
"double locks" and an oligonucleotide nanovehicle
(ONV) functionalized with a hairpin construction as
the "smart key". The "lock" can be opened after
hybridization and cleavage of the hairpin, enabling
the release of siRNA into the cells [88].
DNA origami, a DNA-based nanostructure
composed of multiple building blocks, has played a
significant role in advancing the field of DNA
nanotechnology, particularly in biomedical applica-
tions. This is due to the ability of DNA origami to be
functionalized with various groups, including
functional nucleic acids. By incorporating nucleic acid
aptamers into DNA origami, targeted delivery of
cargo can be achieved, enhancing its potential in
biomedical applications [89]. In recent developments,
researchers have successfully created a DNA
nanorobot designed for intelligent drug delivery. This
nanorobot is engineered to carry the enzyme
thrombin within its structure. On the surface of the
nanorobot, an aptamer known as AS1411 is
introduced, which specifically binds to a protein
called nucleolin that is expressed in tumor cells. Upon
reaching the targeted tumor site, the DNA nanorobot
can be triggered to open and release the thrombin
payload. The released thrombin then initiates blood
clotting processes, resulting in tumor necrosis and
suppression of tumor growth. This innovative
approach holds great promise for safe and precise
drug delivery in cancer therapy, offering potential
advancements in the field [90]. While several studies
have shown the efficacy of using DNA origami
nanostructures for drug delivery, there is still
potential for further exploration of their use in
therapeutics as the building blocks of origami. In a
study, researchers used nanocarriers with DNA
origami (Apt-DOX-origami-ASO) to deliver chemo-
therapy drugs and antisense oligonucleotides (ASOs)

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for the treatment of drug-resistant cancer cells. The
Apt-DOX-origami-ASO nanocarrier developed by
Pan et al. consists of a DNA origami structure that is
functionalized with staple strands protracted with
MUC1 aptamer, which gives it targeting capability.
The origami can carry ASOs by strand hybridization
and has the DOX loaded onto it through electrostatic
adsorption. This nanocarrier showed promising
results in terms of controlled drug release and gene
silencing (Figure 1D-F) [91].
DNA nanostructures are typically made up of
many nucleic acid (NA) sequences, which result in a
great number of intrinsic nicks in the phosphodiester
bonds of the DNA. These nicks increase the instability
of the DNA structures by providing more high sites
for cleavage by nucleases. To address this issue,
Figure 1. Working principles of engineered DNA nanomachine. (A) Schematic illustration of the working mechanism of DNA-based nanomachine. Structure of DNA-based
nanomachine, and the aptamer DNA nanomachine for cell surface computing: the binding of two aptamers to their biomarkers and releasing cS and cF from recognition toes. (B)
PAGE results established the assembly of the DNA-logic gate TP. Lane 1: DNA TP scaffold. Lane 2: F/S/R-TP. Lane 3: sgc8c/cS-TP. Lane 4: sgc4f/cF-TP. Lane 5:
sgc8c/cS-sgc4f/cF-TP. Lane 6: F/S/R-sgc8c/ cS-sgc4f/cF-TP. (C) Dynamic light scattering (DLS) results for determination of the size of 500 nM TP scaffold (red) and DNA-logic gate
TP (blue). Reprinted (adapted) with permission from [78]. Copyright 2018 American Chemical Society. (D) The design of Apt-DOA with 12 MUC1 aptamers, Bcl2, and 28 P-gp
ASOs, targeted co-delivery of ASO and DOX to improve therapy in drug-resistant cancer cells. (E) Schematic illustration of the synthesized Apt-origami-ASO dispersed in PBS
buffer. (F) Dox-release profile of Apt-DOA in PBS buffer. Reprinted (adapted) with permission from [91]. Copyright 2020 American Chemical Society.

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researchers have developed strategies for
constructing DNA nanostructures using a few DNA
strands, reducing the number of potential cleavage
sites and increasing the structures' stability. In 2013, a
group of researchers led by Zhu established
self-assembled nanoflowers (NFs) by the rolling circle
amplification (RCA) technique. These NFs are made
up of non-nicked building blocks that are densely
functionalized, which allows them to be prepared
using only a few DNA strands. This design overcomes
the problems of intrinsic nicks that can affect the
stability of the nanostructures and the complexity of
their preparation. NFs are attractive biomaterials due
to their ease of synthesis and good compatibility, and
they have been explored for various biological
applications [92, 93]. Scientists have developed a
DNA NF that can be used to deliver drugs specifically
to cancer cells. These NFs, called Sgc8-NFs-Fc, are
made of artificial analogues, and can be made in sizes
ranging from 50 to 1000 nanometers. They can be
degraded and release the drug they carry when
exposed to hydrogen peroxide. They also comprise
aptamers, which allow them to bind to and enter
cancer cells. In both lab and animal studies, the
Sgc8-NFs-Fc NFs showed good targeting efficiency
against tumors, making them a promising tool for the
cancer drug delivery [94].
DNA-based micelles/polymer
Micelles are self-assembled molecules with a size
ranging from 10 to 100 nm. They consist of a
hydrophilic shell and a hydrophobic core, making
them suitable for drug incorporation. The hydrophilic
shell serves to prevent drug loss and evade the
opsonization process triggered by the complement
system, which otherwise leads to the rapid clearance
of drugs from systemic circulation [95, 96]. Scientists
have successfully developed a nanostructure known
as spherical DNA micelle, composed of amphiphilic
oligonucleotides that can undergo self-assembly.
These DNA micelles exhibit a multivalent effect,
which significantly enhances their capacity to bind to
specific targets using aptamers. As a result, they hold
great potential for applications in drug/gene delivery
systems and biosensors [97]. Researchers have
developed a technique for producing targeted
aptamer-lipid micelles by connecting aptamer and
lipid compounds using a methacrylamide branch.
When exposed to adequate light, these components
form a covalent bond, resulting in the formation of
aptamer-lipid micelles. This innovative approach
enhances the stability of the micelles and opens up
possibilities for their utilization in imaging
applications [98]. In another study, researchers
designed aptamer-based micelles for cancer-targeted
chemodynamic therapy (CDT). These micelles are
made of amphiphilic oligonucleotides and contain
hydrophobic prodrug bases. When activated, they
generate toxic radicals in cancer cells. This approach
offers a new method for designing aptamer-based
micelles for cancer therapy. It overcomes the high
dependence on tumorous hydrogen peroxide and the
strong acidity required for classical Fenton or
Haber-Weiss chemistry in CDT [99].
Among the various nanomaterials, polymers
have garnered significant attention due to their
structural diversity, allowing for the attainment of
different sizes, morphologies, and desirable surface
properties. Polymers can be employed as imaging
agents, offering advantages such as long half-life, high
stability, compatibility, and increased tissue density
[100]. Biodegradable polymer-based nanomaterials
propose appropriate applications in the drug/gene
delivery systems, cancer therapy, and biomedical
fields [101]. By replacing the hydrophobic portion of
oligonucleotides with polymers, including poly(d,l-
glycolic acid) and poly(d,l-lactic acid), researchers
have created multifunctional polymer nanostructures
that can be loaded with drugs. These nanostructures
have potential applications in biotechnology. Resear-
chers have developed nanostructured coordination
polymers (NCPs) for use in photodynamic therapy
(PDT). These polymers are composed of aptamer
AS1411 and contain photosensitizer chlorine e6 and
deoxyribozyme hemin. They have been modified with
polyethylene glycol (PEG) and are referred to as
Ca-AS1411/Ce6/hemin@pHis-PEG (CACH-PEG)
NCP nanostructures. Studies have shown that
coordination polymers with combined several
therapeutic elements, such as CACH-PEG, can bind to
and internalize into the nucleus of cells. To synthesize
CACH-PEG, the AS1411 aptamer was first utilized to
form a G quadruplex structure and loaded with Ce6
and hemin, resulting in AS1411/Ce6 with a size of
less than 10 nm. Next, organic ligands AC and AH
were mixed with CaCl2, along with pHisPEG as a
stabilizing agent, to form CACH-PEG (Figure 2). The
CACH-PEG nanostructure displayed a spherical
morphology (Figure 2). Following the injection of
CACH-PEG and subsequent imaging using a Lumina
III in vivo imaging system, the accumulation of Ce6
signals in the tumor was observed after 8 hours,
indicating the highly effective tumor retention of the
CACH-PEG nanostructure. Furthermore, when mixed
with 99mTc, the CACH-PEG nanostructure could be
chelated into the center of the porphyrin in Ce6,
demonstrating excellent radiolabeling stability for in
vivo applications [102]. The G-quadruplexes and
hemin within the polymer then exhibit DNAzyme
activity, decomposing tumor endogenous hydrogen

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peroxide to generate oxygen to further reduce
hypoxia-related resistance. These multiple therapeutic
elements enhance the ability of the polymer to kill
cancer cells.
Figure 2. Synthesis and properties of Ca-AS1411/Ce6/hemin@pHis-PEG Nanocomplexes (CACH-PEG). (a) Illustration depicting the preparation of CACH-PEG. (b, c)
Transmission Electron Microscopy (TEM) image (b) and Scanning Transmission Electron Microscopy (STEM) mapping (c) of CACH-PEG Nanocomplexes. (d) Hydrodynamic sizes
measured by Dynamic Light Scattering (DLS) and a photograph (inset) of CACH-PEG dispersed in water, PBS, buffer, and DMEM cell-culture medium. (e) UV-visible-near-infrared
(UV–vis–NIR) spectra of Ce6, hemin, and CACH-PEG. (f) Generation of oxygen in 2 mM H2O2 solutions after adding AS1411/hemin (AH) complex or CACH-PEG
Nanocomplexes at room temperature. (g) Light-triggered generation of singlet oxygen measured by increased SOSG fluorescence for free Ce6 CDCH-PEG or CACH-PEG
under 660 nm light irradiation in the absence or presence of H2O2. (h, i) TEM images of CACH-PEG after overnight incubation in PBS at (h) pH 7.4 or (i) pH 5.5. (j) Hydrodynamic
sizes of CACH-PEG after incubation in PBS at pH 7.4, 6.5, or 5.5 for 1 hour. Reprinted (adapted) with permission from [102]. Copyright 2018 American Chemical Society.

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Other researchers have designed DNA aptamer-
hyperbranched polymers to accurately control drug
delivery, which can enhance the biostability of
aptamers. Aptamer-Polyprodrug conjugates have also
been developed by connecting a compatible brushlike
backbone to drug delivery systems. In a study, a
ferrocene-comprising NA polymer for drug delivery
against tumors was reported. The size of this polymer
can be tuned through the Fenton-like reaction of
ferrocene moieties in the tumor site, leading to size
shrinkage down to 10 nm. The ferrocene loaded onto
the NA polymer can release great toxic radicals to
destroy tumor cells, improving the targeting
efficiency of the polymer through increased
permeability and enabling the nano-drug to penetrate
deeper into tumors [102-105].
DNA hydrogel
Functional DNA hydrogels, composed of DNA
and possessing enhanced mechanical properties, have
been developed for diverse biotechnology applica-
tions. These DNA hydrogels exhibit excellent water
content and demonstrate high biocompatibility,
rendering them suitable for a wide range of appli-
cations. Furthermore, the DNA modules integrated
within the hydrogel exhibit unique recognition
capabilities, enabling them to target biomarkers
present on the surface of cells [106, 107]. Recently,
several studies have highlighted the significant
potential of DNA hydrogels in cancer therapy. These
hydrogels possess desirable characteristics such as
biodegradability, compatibility, and programmability
of DNA molecules [107]. Besides, DNA hydrogel has
high stability in the serum than other DNA structures.
DNA hydrogel can be formed by simple RCA [108].
Thus, they are considered to have potential in drug
delivery systems according to their biocompatibility
and stability. However, enhancement of large-scale
chemical synthesis of DNA is required to reduce
production costs. Generally, in order to avoid side
effects, the biological properties of such DNA
sequences should be considered in hydrogel design.
This type of DNA hydrogels can be used as a very
promising new biological material in medical
applications.
These hydrogels can be engineered to respond to
stimuli, enabling them to deliver functional cargo
[109]. For instance, researchers have developed
stimuli-responsive and aptamer-based DNA hydro-
gels that can be applied for targeted gene regulation.
Researchers have developed DNA nanohydrogels by
using three compounds, including Y-shaped
monomer B (YMB), Y-shaped monomer A (YMA),
and a DNA linker. These compounds have three, one,
and two sticky ends, respectively, which allow them
to hybridize and form nanohydrogels. The size of
these nanohydrogels can be controlled by adjusting
the ratio of YMA to YMB. The researchers also
incorporated aptamers and GSH-responsive linkages
into the three units to fabricate aptamer-modified
hydrogels that are applied for controlled gene
delivery. These nanohydrogels showed effective
internalization and high biocompatibility, exhibiting
inhibition of cell proliferation with non-toxicity for
normal cells. Besides, therapeutic genes can be
effectively released from hydrogels for angiogenesis
[110, 111]. Researchers have developed hydrogels
based on dual aptamers that can co-deliver two
growth factors, VEGF and PDGF-BB, to promote
angiogenesis. These hydrogels are assembled in situ
after injection by aptamer-functionalized fibrinogen,
which provides shelter for the delivery of the growth
factors. Using multiple growth factors in this
codelivery strategy is effective in promoting
angiogenesis [112]. In a separate study, a DNA
poly-aptamer hydrogel was developed for gene
therapy of cancer using CRISPR/Cas9 and immune
checkpoint-blocking DNA aptamers. This hydrogel
allows for the targeted delivery of gene editing and
immune-modulatory agents to cancer cells,
potentially providing a novel treatment method for
cancer. A DNA aptamer hydrogel was created
through an RCA process using a DNA strand with an
aptamer against PD-1 and a sgRNA. The release of the
PD-1 from the hydrogel was facilitated by the precise
cutting action of Cas9/sgRNA, causing the
obstruction of PD-1 and activation of the secretion of
cytokine for splenocytes [113]. This demonstrates the
potential of hydrogel in immunotherapy.
Researchers have explored the use of hydrogel
based on aptamer to assemble cells, which could have
applications in cancer diagnosis and cell-based
therapies. In a recent study, a hydrogel based on
aptamer was designed to capture circulating tumor
cells (CTCs) using aptamer-triggered clamped
hybridization chain reaction (atcHCR). This hydrogel
can selectively capture CTCs from a blood sample,
potentially enabling the detection and analysis of
these cells for the diagnosis and treatment of cancer. A
DNA strand made up of an EpCAM aptamer was
used to recognize CTCs in a hydrogel using an
atcHCR (Figure 3A). In fact, Figure 3 showed the
binding of aptamer and EpCAM on the cell surface
[cy3 (red) and DiO (green)]. The CTCs could be
captured without significant damage and
subsequently released for culturing and analysis by
exposure to specific chemical stimuli [114]. A separate
study developed a DNA network to deliver bone
marrow mesenchymal stem cells (BMSCs) without
damaging the cells. This network was created through

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double RCA and self-assembly of two long DNA
strands. The insertion of aptamers was done into
DNA-strand-1 to allow to capture BMSCs, while
DNA-strand-2 was applied to hybridize with chain-1
and fabricate a 3D structure to enclose the cells
(Figure 3). The BMSCs could be released by digesting
the DNA network with nuclease, with only minimal
impact on cellular activity [114, 115].
Figure 3. (A) DNA gelation-based cloaking and decloaking of CTCs. (a) The aptamer-initiator blocks were capable of binding to the EpCAM. (b) Confocal images of
aptamer-initiator blocks (red) colocalized with DiO-stained lipid (green). (c) The 3D structure of MCF-7 cells is shrouded in DNA hydrogel, which displays multilayered cells in
the hydrogel. (d and e) When ATP was added, the MCF-7 cells were released. Reprinted (adapted) with permission from [114]. Copyright 2017 American Chemical Society. (B)
(a) Design of a DNA network for stem cell fishing. (b) Formation procedure of DNA chains by RCA to attain a 3D network. (b) Combination of DNA chains to envision molecular
diffusion throughout the fabrication of the DNA network. (c) The mechanism of capture includes capture, envelop and release. Reprinted (adapted) with permission from [115].
Copyright 2020 American Chemical Society.

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DNA-functionalized liposomes
In general, liposomes are small and spherical
structures that have a cell membrane-like structure
and a large cavity that can be loaded with various
types of molecules and drugs [116]. The multilayered
spherical structures of liposomes with 50–500 nm in
diameter particle size is greatly rich in lipid contents
with different principles for their structural
properties, their size and formation process, as well as
drug loading [117]. These properties make them
appropriate for different applications, including
drug/gene delivery, diagnosis, and cancer therapy
[118-120]. Theranostic dual-layered nanomaterial
made by adding a liposomal layer to Au-PEG showed
in vivo high stability. Functionalized nanomaterial is
stable in physiological conditions, and the 64Cu
labeled Limulus amebocyte lysate (LAL) platform
displays sufficient blood circulation properties and an
efficient tumor targeting capability of 16 %ID/g [118].
Nevertheless, the non-specific nature of cargo
delivery by liposomes can be a limitation. For
example, it can be difficult to deliver drugs via
liposomes to targeted cells without any toxicity. In
2010, researchers established a liposome system based
on aptamers for targeted drug delivery, which allows
for the precise delivery of drugs to targeted cells while
reducing the impact on normal cells. In this approach,
sgc8 aptamers were used to enable the delivery of
liposomes to target cells by specifically recognizing
and binding to proteins on the surface of the target
cell membrane. The use of aptamer modification
allowed for greatly effective drug delivery. Recently,
functional NAs have been packaged into liposomes
for cancer therapy. Researchers established an
aptamer-based liposome platform for the delivery of
miRNAs. The platform was modified with EpCAM
aptamers, demonstrating high effective internaliza-
tion efficacy and inhibiting tumor growth (Figure 4A).
The synthesis of liposome-aptamer was accomplished
using the thin film hydration method. Subsequently,
miRNA was loaded into the nanoparticles, specifically
the EpCAM Apt-HSPC/DOTAP/Chol/DSPE-
PEG2000-COOH (ANPs), through the self-assembly
method. The results demonstrated that the liposomes
synthesized exhibited a round appearance and
dispersibility (Figure 4B). Furthermore, targeted
delivery of the ANPs to colon cancer cells expressing
EpCAM on HCT116 cells, Hela cells, and HCT8 cells
was developed. It was observed that a stronger
fluorescent signal was detected in HCT116 cells and
HCT8 cells compared to HeLa cells, indicating the
selective delivery of MANPs (Figure 4D) [121]. As
shown in Figure 4D, they observed the signal of
DiR-ANPs in tumor tissues at 24 h. Furthermore, the
signal of DiR-ANP stayed in the tumor for 2 days after
the intravenous injection, while no signal was
observed in the other groups. These nanoplatforms
have the potential to perform as effective carriers to
increase targeted therapeutic abilities. In addition to
traditional chemical liposomes, mimetic liposomes
made by extruding or secreting cells can also be
prepared with aptamers for use in therapeutics. A
delivery platform was developed with drugs,
aptamers, and liposomes for cancer therapy. The
biomimetic liposomes, derived from cells, were used
to encapsulate and release drugs to cells through
membrane fusion. This delivery platform effectively
encapsulates and delivers a drug to the photodynamic
and photothermal therapy [121-124].
Aptamer-based liposomes have the potential to
release CRISPR/Cas9 complexes into specific cells for
gene editing. For instance, researchers developed a
liposome-CRISPR/Cas9 system based on aptamers
for the delivery of sgRNA to permit the therapeutic
application of the Cas9/sgRNA vector. This platform
comprises an aptamer that binds to prostate cancer
cells, which was able to decrease the expression of
mRNA by approximately 60% in vitro, demonstrating
significant cell-type binding ability. In addition, in
vivo studies showed that gene silencing improved a
noticeable deterioration of prostate cancer, providing
future promise for the synthesis of aptamer liposome
platforms for CRISPR/Cas9 delivery. Another study
used an aptamer-modified lipopolymer to regulate
the VEGFA gene in osteosarcoma. The aptamer LC09,
which targets osteosarcoma, was applied to
lipopolymer-containing CRISPR/Cas9 plasmids.
Besides, LC09 can facilitate the sensitive distribution
of CRISPR/Cas9 in orthotopic osteosarcoma and also
inhibits osteosarcoma and lung metastasis.
LC09-PPC-CRISPR/Cas9, also reduced expression of
VEGFA and markers of proliferation and metastasis
in lung metastatic sites [125-127].
Aptamer-embedded inorganic
nanomaterials
Nanomaterials that have been modified with
specific aptamers have proven useful in different
areas of biomedicine, such as biosensing, targeted
drug delivery, cancer diagnosis, and treatment. This
text will provide an overview of four inorganic
nanomaterials with aptamers embedded in them,
including carbon, gold, magnetic nanomaterials and
metal-organic frameworks (MOFs). These materials
have seen recent advancements in their use for
diagnostic and therapeutic purposes.
Gold-based nanomaterials
Gold nanomaterials have exceptional properties,
and they can be used in bioapplications, including

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photoluminescence, light scattering, photothermal
conversion, thermodynamic stability, biocompati-
bility, the ability to carry cargo, and the ability to be
easily modified. These characteristics have led to
using gold nanomaterials as building blocks in
functional nanoplatforms [128, 129]. For instance,
aptamer-modified gold nanoparticles can be used as
electrochemical and colorimetric biosensors for
analysis. One study developed a sensor for the
colorimetric detection of exosomal proteins using
aptamers against exosome proteins against gold
nanoparticle aggregation. In the existence of
exosomes, the aptamers bind to proteins, leading to
the release of free gold nanoparticles that rapidly
aggregate and cause a color change that can be
observed in a short time. This provides a quick
sensing system for the early diagnosis of diseases
[128]. Another research has used aptamer-based gold
nanomaterials to quantify intracellular adenosine
triphosphate in cells and to efficiently kill cancerous
cells through targeted drug delivery. Gold or its
composites functionalized with aptamers have also
been established for photothermal cancer therapy and
cancer radiation therapy. These nanoplatforms can be
applied as an effective approach for intracellular
quantification of other molecules that use aptamer
binding to remove a biological response [130].
PAMAM dendrimers, a type of synthetic
polymer capable of encapsulating drugs and metal
nanomaterials like gold nanoparticles, have been
investigated by researchers for their theranostic
potential. The study focused on a curcumin-loaded
dendrimer-gold nanostructure. The dendrimer-gold
hybrid was created by combining AuCl4- ions with
PEGylated amine-terminated generation 5
poly(amidoamine) dendrimers. To achieve targeted
binding to colorectal adenocarcinoma cells, the
system was conjugated with the MUC-1 aptamer. The
results demonstrated the accumulation of the
theranostic agent in HT29 and C26 cells, showing
greater toxicity compared to the non-targeted system.
Moreover, in vivo experiments showcased the high
Figure 4. Schematic of the fabrication of NPs and ANPs. (A) Mechanism to form NPs and ANPs. (B) TEM image of MANPs and MNPs. The results showed the round-shaped
morphology of liposomes. In vivo biodistribution of ANPs. (C) In vivo distribution of ANPs after intravenous injection for 1-48 h. (D) Fluorescence images of HCT116 cells,
SGC7901 cells, and HeLa cells incubated with MANPs for 6 h. The scale bar is 200 μm. Reprinted (adapted) with permission from [121]. Copyright 2019 American Chemical
Society.

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potential of the theranostic system in CT-scan tumor
imaging and cancer therapy. Twelve hours after the
administration of Apt-PEG-AuPAMAM-CUR, the CT
scan images of the treated group exhibited a higher
signal value in the tumor tissue. These findings
highlight the efficacy of this therapeutic platform and
its considerable potential in combating colorectal
cancer adenocarcinoma [131].
Carbon-based nanomaterials
Carbon nanomaterials, including carbon
nanotubes, graphene and graphene oxide (GO) and
their hybrids, have been extensively researched due to
their exclusive properties, which make them useful
for imaging and biomedical applications [132].
Carbon nanomaterials can be paired with aptamers to
act as electrochemical sensors for cancer diagnosis
and treatment when appropriately functionalized. For
instance, a recent study established a graphene-hemin
nanosystem comprising gold NFs with high catalytic
activity. When aptamers that connect to K562
leukemia cancer cells were introduced, the nano
platform could detect the target cells with high
sensitivity. Additionally, aptamer-based graphene
nanomaterials can be used to analyze cell membrane
surface and intracellular biomarkers [133]. A
multifunctional theranostic platform has been
developed, utilizing the conjugation of porphyrin (P)
derivatives with high oxygen production activity,
aptamer-functionalized graphene quantum dots
(GQDs), and PEG. This platform has exhibited
favorable compatibility and low toxicity. Notably, the
intrinsic fluorescence of GQDs enables the
differentiation between cancer cells and somatic cells.
Additionally, the high surface area of the platform
facilitates gene delivery for the detection of
cancer-related microRNA (miRNA). Furthermore, this
system demonstrates remarkable photothermal
conversion efficacy, reaching up to 28.5%, along with
a high quantum yield of oxygen production.
Consequently, it proves to be suitable for progressive
photothermal and photodynamic therapies [134].
Metal-organic framework-based
nanomaterials
MOFs are a group of coordination nanomaterials
with a range of unique properties and can be used in
various fields, including catalysis, biosensors and
biomedical applications [8, 135]. MOFs can be easily
functionalized and have a high capacity for the cargo
loading, making them suitable for combining with
aptamers. As a result, different aptamer-based MOF
platforms have been developed for cargo delivery in
cancerous tissues [136]. For instance, aptamers that
bind to specific molecules can be intended to act for
controlling delivery. Researchers created ATP-
stimulate nanoparticles comprising nanoscale MOFs
(NMOFs) to target the delivery of fluorescent
molecules [137]. The nanoparticles were fabricated
with complementary nucleic acids that hybridized
with an aptamer to lock the nanoparticle and prevent
cargo leakage. After accumulating at the tumor area,
the nanoparticles were unlocked through ATP to
deliver cargoes. The ATP-responsive NMOFs
nanoparticles were also modified with AS1411
aptamers to give them targeting ability and were
shown to precisely deliver the drug to prevent cancer
cell growth. Another type of MOF-based aptamer can
be focused on cell recognition and delivery. Ning and
co-workers developed a surface coordination chemis-
try approach for efficiently immobilizing functional
DNA on the surface of NMOFs, which allowed for the
targeted delivery of therapeutic DNA [138]. On the
other hand, researchers created porphyrinic metal-
organic framework (ZrMOFs) nanoparticles for
imaging by functionalizing the nanoparticles with
phosphate-terminal DNA aptamers. This enabled the
ZrMOF nanoparticles to accumulate in cells
selectively and allowed for targeted imaging and
increased PDT. This strategy may provide new
approaches for functionalizing other types of MOF
nanomaterials [139].
In another study, a unique type of material
called a bimetallic MOF was created by combining
different MOFs to form a hybrid. This method, called
MOF-on-MOF, allows for the properties of both MOFs
to be incorporated, resulting in a material with new,
distinct characteristics. Researchers utilized this new
material, specifically the bimetallic CuZr-MOF, to
support immobilising a biomolecule called aptamer
on the surface of an electrode, forming an
electrochemical aptasensor. This sensor can detect a
biomarker called miR-21 associated with cancer.
Results exhibited that the properties of the CuZr-MOF
could be tailored by varying the order of addition of
the organic linkers. The aptasensor displayed a
greatly sensitive and accurate diagnosis of miR-21,
with a LOD of 0.45 zM. Additionally, the sensor
presented exceptional specificity, and reproducibility,
making it a highly effective tool for early and sensitive
diagnosis of miRNA-related diseases. To evaluate the
precision and sensitivity of the aptasensor, the
detection and quantification limits were determined
by exposing the Apt/CS-CuZr-MOF/GCE to a range
of concentrations of miR-21 in PBS (pH 7.4). As the
concentration of miR-21 increased, the current
generated by the sensor decreased as more miR-21
strands bound to the aptamer strands, hindering the
electron transfer to the electrode surface. The
detection and quantification limits were determined

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using the square-wave voltammetry (SWV)
technique. The results exhibited that the aptasensor
had a linear response to miR-21 concentrations from 1
zM to 1 pM, with a high correlation coefficient (R2) of
0.99. The lowest miR-21 concentrations that could be
detected and quantified by the aptasensor were 0.45
and 1.5 zM, respectively, which demonstrates its high
sensitivity and precision [140].
In a research effort, scientists have developed a
method for targeted anti-tumor drug delivery using a
unique combination of materials. They utilized
zirconium-based MOFs (Zr-MOF) embedded with
silver nanoclusters (Ag NCs) and employed an
aptamer called AS1411 as a guide to target cancer
cells. The resulting system was called UiO-66@
AgNCs@Apt. They also created a variant of this
system, called UiO-66@AgNCs@Apt@DOX, which
incorporated the cancer drug DOX and was designed
to show increased loading efficiency of around 90%
and controlled release of the drug for up to 96 hours.
The study exhibited that the aptamer-modified
delivery system could effectively target and be taken
up through cancer cells with over 80% specificity
using confocal laser scanning microscopy. They also
tested the system on cancerous and non-cancerous
cells and found that the drug is effectively delivered
to cancer cells, specifically with a cellular uptake of
around 30% more. The system shows a robust
enhancement of anti-tumor effect with low
cytotoxicity in an extensive range of concentrations
from 5-50 µg/mL, making it a promising candidate
for controlled drug delivery in cancer therapy.
Scientists studied the ability of UiO-66@AgNCs@
Apt/DOX to selectively kill cancer cells and spare
normal cells using an in vitro assay, comparing their
effectiveness on MCF-7 cells to normal L929 cells.
They found that both formulations had low toxicity at
high concentrations. Still, the UiO-66@AgNCs@Apt/
DOX composite was more effective at killing
cancerous and normal cells with an inhibition rate of
73.3% and 64.4%, respectively, at 5 µg/mL. The
one-pot encapsulated UiO-66@AgNCs@Apt@DOX
had greater cytotoxicity on MCF-7 cells with an
inhibition rate of 80.3% at 10µg/mL; however, it had a
lower rate of 54.9% on L929 cells at the same
concentration. This discrepancy may be due to the pH
and environment within the endosomal compartment
of cancer cells and the specificity of aptamer
modification that enhance the targeted binding to
MCF-7 cells by specific internalization. These results
indicate that UiO-66@AgNCs@Apt@DOX has a
higher potential for the selective cancer cell [141].
Researchers have successfully developed a novel
method for imaging and drug delivery targeted
specifically towards triple-negative breast cancer, a
form of cancer commonly treated with chemotherapy.
This breakthrough was achieved through the creation
of a unique nanocarrier, referred to as Fe3O4@MOF-
DOX-CDs-Apt, consisting of an anti-cancer drug,
fluorescent carbon dots (CDs), and an aptamer. The
nanoplatform is constructed by combining a
nucleolin-DNA aptamer with a magnetite core and a
MOF shell. For fluorescence imaging purposes, CDs
are encapsulated within the Fe3O4@MOF nanocompo-
site, thereby imparting fluorescence properties. The
resulting Fe3O4@MOF nanostructures exhibit a
monodisperse morphology and possess a size of 17
nm. The nanocarrier would release its drug payload
specifically in the existence of certain cancer cells,
which overexpress a protein called nucleolin. The
release process was pH dependent, allowing for more
efficient drug delivery. These nanocarriers are more
effective in targeting cancer cells with a specificity rate
of over 85% compared to normal cells. They also
exhibited fluorescence imaging capabilities, which
can be used to monitor their distribution in the body.
Cytotoxicity experiments showed that the carriers
inhibited cancer cell proliferation and induced
apoptosis, with over 77% of MDA-MB-231 cancer cells
killed after 24 hours of incubation. The same
concentration of the nanocarrier has less than 10%
impact on normal HUVEC cells. Therefore, the
researchers propose that these nanocarriers could be a
potential solution for treating triple-negative breast
cancer through their ability to deliver drugs and
image their distribution. The studies suggest that
several mechanisms work together to create a
multi-stimuli-responsive drug delivery system. One
such mechanism is using acid-sensitive UiO-66 MOFs,
which can release drugs in low-pH environments
found in cancer cells. This process was enhanced by
modifying the MOF with amino groups, making it
more sensitive to protonation at a pH below 6.3.
Additionally, aptamers were used to lock the pores of
the MOF, only releasing drugs when they bind to a
specific target, such as a protein overexpressed on
MDA-MB-231 cancer cells. The system also includes a
magnetic core, which could have the potential for
magnetic-responsive drug delivery, although this
aspect still needs to be fully studied in these
experiments [142].
Magnetic-based nanomaterials
Magnetic nanomaterials with functional mag-
netic abilities can be used in biosensors, delivery
systems, biosensing systems and the separation of
specific cells. Promising physiochemical properties
and the ability to accommodate targeting moieties
make superparamegnetic iron oxide nanoparticles
(SPIONs) appropriated as theranostic agents [143].

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Aptamer-functionalized magnetic nanomaterials,
which have high selective recognition and binding
abilities, have become influential in capturing and
separating biological samples. One recent example of
aptamer-functionalized magnetic nanomaterials
being used for cell isolation is the detection of CTCs
for clinical diagnostic purposes. Polyethylenimine
(PEI)- stabilized Fe3O4 nanoparticles encapsulated
inside PEI/poly(vinyl alcohol) nanofibers. After a
treatment needed for the magnetic short nanofibers
(MSNFs), surface conjugation of the aptamer was
done. The aptamer-MSNFs, with a size of 350 nm,
showed the capturing cancer cells with an efficacy of
87% and allowed the release of cancer cells with a
high efficacy of 90% after nuclease treatment.
Especially, this aptamer-MSNFs showed a critically
greater release efficacy compared to the commercial
magnetic beads [144] (Figure 5A).
Ding et al. developed a nanoplatform that used
near-infrared (NIR) Ag2S dots with aptamer
modification and the encapsulation of magnetic
nanoparticles in a cell membrane to efficiently isolate
and detect CTCs. The nano-bio-probe had a great
capture efficiency of 97 % and purity for CTCs of 96%
and could also be applied to detect CTCs in blood
samples. Researchers established a technique for
capturing and releasing CTCs using aptamer-based
magnetic nanofibers. Aptamer-based magnetic
nanomaterials have also been discovered for the
separation of CD8+T cells. Researchers produced a
DNA aptamer based on SELEX and used it to separate
CD8+T cells at high yields with properties. This
demonstrates the effective potential of aptamer-based
magnetic nanoparticles in the traceless isolation of
lymphocyte subsets [144-148].
In another study, researchers developed
superparamagnetic iron oxide nanoparticles (SPIONs)
coated with gold nanoparticles (Au NPs) for the
purpose of magnetic resonance imaging (MRI) and
photothermal therapy of colon cancer cells. The
formation of SPIONs was achieved through a
microemulsion method. The inclusion of Au NPs
served to reduce the cytotoxicity of SPIONs and
enhance their photothermal capabilities. To act as a
targeting agent, the thiol-modified MUC-1 aptamer
was conjugated onto Au@SPIONs, allowing for
binding and synergistic affinity. MTT results demons-
trated that the nanostructure exhibited minimal
toxicity within the concentration range of 10-100
μg/ml, indicating lower cytotoxicity compared to
bare nanoparticles. MR imaging revealed significant
contrast enhancement in vitro, indicating that SPIONs
could be utilized as effective contrast agents. Further-
more, cells treated with Apt-Au@SPIONs exhibited a
higher death rate compared to the control group
when subjected to near-infrared (NIR) irradiation.
These developed nanomaterials hold promise as
theranostic agents for MR imaging and photothermal
therapy of colon cancer cells [143].
However, the combination of chemotherapy
with magnetic hyperthermia holds promise as a
strategy for cancer therapy. Nonetheless, the
nonspecific accumulation of magnetic nanoparticles
has limited their applications. To address this,
researchers have developed a highly selective
theranostic nanosystem called ZIONO-PAMAM-PEG
(ZIPP)-Apt:DOX/siHSPs, designed for theranostic
drug/gene delivery and magnetic resonance
imaging-guided magnetochemotherapy. The cellular
uptake of the nanoplatforms has been significantly
enhanced through the AS1411-nucleolin affinity,
while also achieving a simultaneous reduction of
HSP70/90 to sensitize magnetic hyperthermia and
chemotherapy. Following intravenous injection, the
nanoplatform successfully accumulates in tumor
areas as confirmed by NIR and T2-weighted MR
dual-modality imaging (Figure 5B-C). To ensure lyso-
some escape, dendrimers with proton sponge proper-
ties were utilized. Furthermore, the downregulation
of HSP70/90 via siRNAs sensitized cancer cells to
hyperthermia and chemotherapy. Intriguingly,
intracellular hyperthermia was stimulated, leading to
the rapid delivery of therapeutic drugs such as DOX
and resulting in HSP70/90 exhaustion that further
sensitized magnetochemotherapy. This study demon-
strates the promising potential of magnetic nanopar-
ticles in theranostic drug and gene delivery, as well as
their application in imaging and magnetochemo-
therapy for cancer treatment [149]. Table 1 showed
several recent studies about the role of aptamer-based
nanomaterials in theranostic applications.
Conclusion and future perspectives
Aptamer-based nanomaterials have revealed
exclusive capabilities in diagnostic and therapeutic
applications and have been extensively studied. This
review discusses some recent developments in
biological applications of DNA nanomaterials
embedded in aptamers. Aptamers' ability to recognize
and bind to specific targets, from molecules to cell
lines, has contributed significantly to the development
of aptamer-based nanomaterials in biomedical fields,
such as targeted cell imaging and drug delivery, and
cancer diagnosis and therapy. Aptamers and DNA
nanostructures, both advanced platforms for
biomedical applications, have unique properties that
are utilized in various fields. However, they
demonstrate even more potential when integrated
into areas such as biosensing, imaging and targeted
drug/gene delivery.

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Figure 5. Design of DNA Aptamer- Magnetic Nanofibers for Effective Capture of CTC. (A) schematic shows the surface modification of MSNFs for the capture of cancer cell.
Reprinted (adapted) with permission from [144]. Copyright 2019 American Chemical Society. Sensitized magneto-chemo theranostics and NIR/MR dual-modality imaging. (B).

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Accumulation of the ZIPP with AS1411 in the tumor after 8 h. (C) The MRI signal ratio of tumor to the muscle is reliable with the accumulation rate detected from NIR imaging
that ZIPP-Apt was efficiently reserved in the tumor area and triggered a signal decrease at 24 and 48 h after injection. Reprinted (adapted) with permission from [149]. Copyright
2021 American Chemical Society.
Table 1. Different types of aptamer-based nanomaterials in multiple theranostic applications
Nanomaterials
Aptamers
Conjugation
method
Theranostic
applications
Descriptions
Ref
ALGDG2
AS1411
aptamer
Covalent amide
bonds
Cancer therapy
AS1411-liposome-PEG-MnO-PTX showed the potential of
simultaneous MRI diagnosis and therapy of renal carcinoma, strong
MR contrast effect in the tumor, high half-life during circulation in
blood, and high potential in tumor growth inhibition.
[150]
SPIONs)/
poly(lactic-co-glycolic acid)
(PLGA)
AS1411
aptamer
Covalent carboxy
linkage
Cancer imaging and therapy
Aptamer conjugated nanoparticles increased cellular uptake of DOX in
C26 cancer cells, increased. the cytotoxicity effect of drug and greater
tumor inhibition in mice bearing C26 colon carcinoma xenografts.
[151]
PAMAM dendrimer
AS1411
aptamer
Amide
condensation
reaction
Bioimaging and drug delivery
This platform act as a dual function of targeting and drug delivery for
in
vitro and in vivo imaging and cancer therapy, with high affinity of
aptamer AS1411 toward cancer cells, and controlled delivery of DOX
into cells
multifunctional
nano-drug delivery systems for precise cancer theranostics.
[152]
Liposomes
AS1411
aptamer
Covalent coupling
reaction
MRI diagnosis and cancer
therapy
AS1411 aptamer can increased the MRI effect and the tumor growth
inhibition, presenting its potential as a theranostic agent for renal
carcinoma.
[153]
QDs-
Anti-EGFR
aptamer
N/A
Theragnosis of triple-negative
breast cancer (TNBC) targeted
drug delivery
EGFR- QLs exhibited increased delivery to target cancer cells, more
effective gene silencing and increased tumor imaging.
[154]
Au@SPIONs
MUC-1
aptamers
Thiol-maleimide
reaction
MR imaging and photothermal
therapy of cancer cells
Aptamer-Au@SPIONs were revealed to have greater uptake in MUC-1
positive cells and higher toxicity than other materials.
[143]
Au@Ag/Au nanoparticles
S6 aptamer
Thiol-maleimide
reaction
Imaging and specific PTT
cancer therapy
S6–Au@Ag/Au nanoparticles could effectively internalization into the
A549 cells, and destruct cells under the N IR irradiation.
[155]
PEG-AuPAMAM-CUR
MUC-1
aptamer
Covalent
conjugation
CT-scan tumor imaging and
cancer therapy
This system showed greater cellular uptake, internalization and high
cytotoxicity in C26 and HT29 cells.
[131]
PEGylated-MoS
2
/Cu
1.8
S
AS1411
aptamer
N/A
Chemo-Photothermal cancer
Therapy/ photoluminescence
imaging (PLI)
This theranostic nanosystem were revealed to have targeted delivery,
excellent photothermal conversion efficiency, and antitumor efficiency.
[156]
Biosensors that utilize aptamer-integrated DNA
nanostructures possess a unique combination of
ultra-high sensitivity and specificity. The precise
addressability of DNA nanostructures allows for
control of the sensor's physicochemical properties,
while aptamers, known for their binding specificity
and affinity, allow for accurate sensing of a wide
range of targets, from small molecules to entire cells.
Signal transduction methods in these sensors are
diverse, including options such as electrochemistry,
fluorescence, atomic force microscopy and visual
readout for point-of-care tests. In the field of
bioimaging, aptamer-integrated DNA nanostructures
are utilized extensively. The compatibility of DNA
nanostructures, and enzymatic resistance make it an
ideal option. Additionally, aptamers selected by
cell-SELEX can discriminate positive target cells from
normal controls, allowing for the quantitatively or
dynamic monitoring of biospecies, including
membrane biomolecules, ATP, metal ions, and
environmental factors that may reside on cell surfaces,
inside cells or in living bodies. The exceptional
specificity against cancer cells, stability in biofluids
and tissue penetration of aptamer-based DNA
nanostructures make them perfect carriers for
targeted drug delivery. Diverse therapeutics agents
can be anchored or encapsulated specifically with
high payload in DNA nanostructures for enhanced or
synergistic therapy. Additionally, dynamic DNA
nanotechnology has enabled the development of
smart nanodevices, which are now being explored for
applications in drug delivery and biological process.
Despite its remarkable progress, aptamer-
integrated DNA nanostructures still face limitations
that need to be addressed. One of the main challenges
is screening high-performance aptamers, which is a
complex, time-consuming, and labor-intensive
process. On the other hand, the SELEX technique is
time-consuming and labor-intensive. Therefore,
researchers are searching for new, simpler methods of
aptamer selection. The competitive non-SELEX
selection utilizes the idea that aptamers can be
selected for a target if two similar targets exist
simultaneously. In this technique, PCR is not needed,
and specific aptamers can be selected. Researchers
were able to successfully select aptamers for influenza
subtypes using this method [157].
Another challenge lies in the stability of both
aptamers and DNA nanostructures, which need
improvement for intracellular and in vivo applica-
tions. For targeted drug delivery, aptamers need
protection from the physiological environment, while
the integrity of DNA nanostructures must be
maintained during transit. Efforts have been made to
enhance stability through engineering aptamers and
DNA nanostructures, as well as employing modified

Theranostics 2023, Vol. 13, Issue 15
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nucleic acids. However, further research is required to
validate their efficacy. Moreover, in vivo applications
raise concerns regarding unwanted "gene regulation"
since DNA strands within DNA nanostructures can
potentially interact with mRNAs or genes. Therefore,
conducting toxicity assessments of aptamer-based
DNA nanostructures is crucial. Furthermore, most
studies on aptamer-based nanomaterials have only
been tested at the animal level, necessitating further
research to ensure their safety for use in clinical trials.
This involves studying their toxicity, impact on
genomics, and in vivo safety. Additionally,
investigating the physicochemical interface between
aptamers and nanomaterials during the construction
process is essential to enhance compatibility and
reduce off-target effects. In the future, improvements
to aptamer-based nanomaterials may involve
increasing the fluorescence excitation/emission
wavelengths of nanomaterials to enhance in vivo
imaging and therapy. Clever surface modifications
and reconstructions of aptamers can also be explored
to enhance the binding capability and stability of
aptamer-embedded nanomaterials for in vivo
applications. As chemistry and materials advance,
aptamer-embedded nanomaterials are likely to find
increased usage in diagnostic and therapeutic
applications. Additionally, the practical use of DNA
nanostructures is hindered by their high cost and low
purity. Another challenge pertains to the utilization of
aptamer biosensors in complex samples for point-of-
care applications. Hence, the transfer of aptamer-
based sensors from the laboratory to biomedical
applications still encounters certain challenges.
While aptamer-integrated DNA nanotechnology
has made significant progress, there are still
challenges to be overcome. Researchers are working
to simplify aptamer selection, enhance the stability of
aptamers and DNA nanostructures, and address
concerns about gene regulation. On the other hand,
aptamers and nature-inspired methods together on a
microfluidic chip can enhance the diagnosis and
long-term monitoring of patients. Regarding therapy,
aptamers and nature-inspired methods, including
exosomes, have a key-lock relationship, where
aptamers target specific cells for drug delivery.
However, the selection process for aptamers is
complicated, and the mechanism of those nature-
inspired methods, including exosomes and
lipid-based vesicle uptake by target cells, is not fully
understood. Research on nucleic acid structures and
scalability is needed to improve aptamer-nature-
inspired therapy. Scalability is particularly important
to make this technology more widely available in
clinical settings. Research on optimizing conditions
for aptamer-nature-inspired targeting is also required
to achieve maximum efficiency and specificity.
Despite these challenges, the field is advancing
and increasing attention and resources are being
devoted to this field, which will accelerate its deve-
lopment and expand the role of DNA nanostructures
in biology and medicine. The integration of aptamers
and DNA nanostructures has the potential to
revolutionize the field of biology and medicine. Their
unique properties and versatility allow for a wide
range of applications, and new and exciting applica-
tions will continue to be discovered in the future.
Abbreviations
Ag NCs: silver nanoclusters; AMD: age-related
macular degeneration; Apt: Aptamer; aptNTrs:
aptamer-tethered DNA nanotrains; ASO: antisense
oligonucleotide; atcHCR: aptamer-triggered clamped
hybridization chain reaction; BMSCs: bone marrow
mesenchymal stem cells; cDNA: complementary
DNA; CDT: chemodynamic therapy; cSELEX: circular
SELEX; CTCs: circulating tumor cells; ds: double-
stranded; DOX: doxorubicin; D-PGM: DNA nanoscale
precision-guided missile; EPR: enhanced permeability
and retention; FE-SEM: field emission-SEM; GC:
guidance/control; GQDs: graphene quantum dots;
LAL: Limulus amebocyte lysate; MRI: magnetic
resonance imaging; Mod-SELEX: modified SELEX;
MOFs: metal-organic frameworks; MSNFs: magnetic
short nanofibers; NA: nucleic acids; NCP: nanostruc-
tured coordination polymer; NFs: nanoflowers; NIR:
near-infrared; NMOFs: nanoscale metal-organic
frameworks; NW: nanowire; ONV: oligonucleotide
nanovehicle; PCR: polymerase chain reaction; PDT:
photodynamic therapy; PEG: polyethylene glycol;
PEI: polyethylenimine; PSMA: prostate-specific
membrane antigen; RCA: rolling circle amplification;
RET: reorganized throughout transfection; ROI:
regions of interest; SELEX: systematic evolution of
ligands by exponential enrichment; siRNA: short-
interfering RNAs; ss: single stranded; STEM: scanning
transmission electron microscope; SPECT: single-
photon emission computed tomography; SWV:
square-wave voltammetry; TEM: transmission
electron microscopy; TPGS: D-ɑ-tocopheryl poly-
ethylene glycol succinate; UCNP: upconversion
nanoparticle; VEGF: vascular endothelial growth
factor; WH: warhead; YMA: Y-shaped monomer A;
YMB: Y-shaped monomer B; Zr-MOF: zirconium-
based MOFs.
Author contributions
N.R., S.C., S.A., and R.N.V. wrote the main
manuscript, conceptualized and finalized the
manuscript. All authors reviewed and approved the
manuscript.

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Competing Interests
The authors have declared that no competing
interest exists.
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Author Biography
Navid Rabiee, Ph.D.,
is working in several fields with a multidisciplinary
approach by blending modern molecular and cellular
biology/biochemical sciences with engineering
principles to design the next generation medical
systems and devices for patient treatment. He is the
pioneer in the field of BioInorganic Chemistry with an
emphasis on CRISPR delivery in assistance of
inorganic nano-vectors. Also, he is the pioneer in
developing high-gravity synthesis methods for
porous (in)organic nanomaterials, to reduce the
synthesis temperature and time, and follow the green
chemistry principles. His work has resulted in the
publication of over 250 peer-reviewed journal articles
in prestigious journals, including Nature, Nature
Medicine, Nature Communications, The Lancet, Nano
Today, ACS Applied Materials & Interfaces,
Biomaterials, Advanced Materials, Advanced
Functional Materials, Advanced Healthcare Materials,
etc., 6 books, and over 20 chapters.
Suxiang Chen received
his Bachelor degree of Agriculture in 2010 in South
China Agricultural University. He then obtained his
Master’s degree in Biotechnology (Advanced) and a
second Master’s degree in Technology and Innovation
Management from the University of Queensland in
2013 and 2014 respectively. Later, he worked in Darui
Biotechonology Co. Ltd and Gene Denovo
Biotechnology Co. Ltd in Guangzhou, China as a core
technician and technical support team member
respectively. He obtained his PhD in Biomedical
Science in 2021 from Murdoch University, Australia
under the supervision of Assoc. Prof. Rakesh N.
Veedu, Prof. Steve Wilton, and Prof. Sue Fletcher. He
has also worked in the Centre for Molecular Medicine
and Innovative Therapeutics, Murdoch University as
a laboratory assistant (2016-2019) and research
assistant (2019-2020), and is currently working as a
post-doctoral scientist (since 2022) in Precision
Nucleic Acid Therapeutics research group led by
Assoc. Prof. Rakesh N. Veedu. His current research
focuses include the development of novel RNA
targeting therapies for tackling Duchenne muscular
dystrophy and solid cancers.
Sepideh Ahmadi,
(Ph.D.), is working on the design and synthesis of
non-viral vectors for the delivery of CRISPR. She has
several original and review articles on this topic in
prestigious journals including Nano Today, Journal of
Controlled Release, Scientific Reports, ACS Applied
Bio Materials, and Acta Biomaterialia. Her work has
resulted in the publication of over 50 peer-reviewed
journal articles in prestigious journals, three books,
and over ten chapters.
Rakesh N. Veedu
is currently an Associate Professor and head of
Precision Nucleic Acid Therapeutics laboratory at
Murdoch University and Perron Institute for
Neurological and Translational Science. He obtained
his PhD in synthetic organic chemistry in 2006 from
the University of Queensland, Australia under the
supervision of Prof. Curt Wentrup after completing
his MSc from Griffith University, Australia. He then
continued his postdoctoral career under the
supervision of Prof. Jesper Wengel at the Nucleic Acid
Center, University of Southern Denmark in the field

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of nucleic acid chemical biology. Later in 2009, he was
appointed as a Research Associate Professor within
the Nucleic Acid Center. He then returned to the
University of Queensland in mid-2010 and established
a functional nucleic acid theranostics research group.
His current research is focused on developing novel
synthetic genes targeting nucleic acid therapeutics
and nucleic acid diagnostics against a range of rare
and acquired diseases. In addition, he is also one of
the co-founders and the director of SynGenis Pty Ltd
and ProGenis Pty Ltd.