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Protein nanoparticles (NPs) are potentially valuable carriers for drug delivery, because they are biocompatible, biodegradable, bioabsorbable, and can be easily designed to perform specific functions with high homogeneity when produced by genetic engineering. We constructed protein NPs based on genetically engineered elastin like polypeptides (ELPs...
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Paclitaxel (PTX) as the most important member of the taxane family is used against a wide range of cancers including breast, ovarian and lung cancers. However, the effectiveness of PTX in clinical practice is limited by its low water solubility and permeability in biological tissues. To address these limitations, PTX is formulated with Cremophor EL...
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... Notably, integrins are overexpressed on resistant tumors and promote cancer progression [118]. The enhanced uptake exhibited by these nanoparticles can pave the way for such nanomedicinebased strategies to overcome cancer drug resistance by specifically targeting overexpressed moieties, e.g., integrins [119]. ...
... Development of tumor microenvironment-targeting nanoparticles [40] Elastin-like polypeptides Engineered polypeptides inspired by natural tropoelastin E. coli BL21(DE3) Antitumor peptide b Genetic engineering b Selective delivery system to colon adenocarcinomas [41] E. coli BLR(DE3) Paclitaxel a / iRGD b Encapsulation a /genetic engineering b Development of active targeting and cell-penetrating nanoparticles [42] E. coli BLR(DE3) Doxorubicin a /cell penetrating peptide b ...
... For the specific delivery of ELP nanoparticles to cancer cells, the targeting and internalization of molecules on ELP particle surfaces can be achieved via a genetic engineering approach. Kobatake et al. constructed an ELP fused with a poly aspartic acid tail (ELP-D) and internalizing RGD (iRGD) for use in targeted drug delivery [42]. The engineered protein fusion produced stable nanoparticles owing to the coacervation of the charged poly aspartic acid chain with ELP at high temperatures. ...
Recently, the potential use of nanoparticles for the targeted delivery of therapeutic and diagnostic agents has garnered increased interest. Several nanoparticle drug delivery systems have been developed for cancer treatment. Typically, protein-based nanocarriers offer several advantages, including biodegradability and biocompatibility. Using genetic engineering or chemical conjugation approaches, well-known naturally occurring protein nanoparticles can be further prepared, engineered, and functionalized in their self-assembly to meet the demands of clinical production efficiency. Accordingly, promising protein nanoparticles have been developed with outstanding tumor-targeting capabilities, ultimately overcoming multidrug resistance issues, in vivo delivery barriers , and mimicking the tumor microenvironment. Bioinspired by natural nanoparticles, advanced computational techniques have been harnessed for the programmable design of highly homogenous protein nanoparticles, which could open new routes for the rational design of vaccines and drug formulations. The current review aims to present several significant advancements made in protein nanoparticle technology, and their use in cancer therapy. Additionally, tailored construction methods and therapeutic applications of engineered protein-based nanoparticles are discussed.
... Polymerbased dendrimers can also be used for this purpose [166,189]. Alternatively, small-molecule anti-cancer drugs can be encapsulated into the hydrophobic core of polypeptide elastinlike nanoparticles, designed to display iRGD as part of their fusion polypeptide [190]. Combining magnetic and gold modalities facilitates delivery of the hybrid nanoparticles to cancer cells due to magnetic field and allows for hyperthermia therapy. ...
Active targeting of tumors is believed to be the key to efficient cancer therapy and accurate, early-stage diagnostics. Active targeting implies minimized off-targeting and associated cytotoxicity towards healthy tissue. One way to acquire active targeting is to employ conjugates of therapeutic agents with ligands known to bind receptors overexpressed onto cancer cells. The integrin receptor family has been studied as a target for cancer treatment for almost fifty years. However, systematic knowledge on their effects on cancer cells, is yet lacking, especially when utilized as an active targeting ligand for particulate formulations. Decoration with various integrin-targeting peptides has been reported to increase nanoparticle accumulation in tumors ≥ 3-fold when compared to passively targeted delivery. In recent years, many newly discovered or rationally designed integrin-binding peptides with excellent specificity towards a single integrin receptor have emerged. Here, we show a comprehensive analysis of previously unreviewed integrin-binding peptides, provide diverse modification routes for nanoparticle conjugation, and showcase the most notable examples of their use for tumor and metastases visualization and eradication to date, as well as possibilities for combined cancer therapies for a synergetic effect. This review aims to highlight the latest advancements in integrin-binding peptide development and is directed to aid transition to the development of novel nanoparticle-based theranostic agents for cancer therapy.
Simple and effective detection methods for circulating tumor cells are essential for early detection and progression monitoring of tumors. The use of DNA aptamer and bioluminescence is expected to be a key tool for the simple, effective, and sensitive detection of tumor cells. Herein, we designed multifunctional protein nanoparticles for the detection of tumor cells using DNA aptamer and bioluminescence. Fusion proteins (ELP-poly(d)-POIs), composed of elastin-like polypeptide (ELP) fused with protein of interests (POIs) via poly(aspartic acid) (poly(d)), formed the protein nanoparticles based on the temperature responsivity of ELP sequences, leading to multiply displayed POIs on the protein nanoparticles. In the present study, we focused on porcine circovirus type 2 replication initiation protein (Rep), which covalently conjugated with DNA aptamers, and NanoLuc luciferase (Nluc), which emitted a strong bioluminescence, as POIs. ELP-poly(d)-Rep and ELP-poly(d)-Nluc were constructed and formed the protein nanoparticles with multiply displayed Nluc and Rep (DNA aptamer) that amplified the bioluminescence signal and tumor recognition ability. Mucin-1 (MUC1)-overexpressing human breast tumor MCF7 cells and MUC1-recognizing aptamer (MUC1 aptamer) were selected as models. The MUC1 aptamer-conjugated protein nanoparticles exhibited a 13.7-fold higher bioluminescence signal to MCF-7 cells than to human embryonic kidney 293 (HEK293) cells, which express low levels of MUC1. Furthermore, the protein nanoparticles could detect up to 70.7 cells/mL of MCF-7 cells from a cell suspension containing HEK-293. The protein nanoparticles with multiple Rep and Nluc show a great potential as a material for detecting CTCs.
Injectable nanocarriers and hydrogels have found widespread use in a variety of biomedical applications such as local and sustained biotherapeutic cargo delivery, and as cell-instructive matrices for tissue engineering. Recent advances in the development and application of recombinant protein-based materials as injectable platforms under physiological conditions have made them useful platforms for the development of nanoparticles and tissue engineering matrices, which are reviewed in this work. Protein-engineered biomaterials are highly customizable, and they provide distinctly tunable rheological properties, encapsulation efficiencies, and delivery profiles. In particular, the key advantages of emerging technologies which harness the stimuli-responsive properties of recombinant polypeptide-based materials are highlighted in this review.
Anti-cancer conventional chemotherapeutic drugs novel formula progress, nowadays, uses nano technology for targeted drug delivery, specifically tailored to overcome therapeutic agents’ delivery challenges. Polymer drug delivery systems (DDS) play a crucial role in minimizing off-target side effects arising when using standard cytotoxic drugs. Using nano-formula for targeted localized action, permits using larger effective cytotoxic doses on a single special spot, that can seriously cause harm if it was administered systemically. Therefore, various nanoparticles (NPs) specifically have attached groups for targeting capabilities, not seen in bulk materials, which then need activation. In this review, we will present a simple innovative, illustrative, in a cartoon-way, enumeration of NP anti-cancer drug targeting delivery system activation-types. Area(s) covered in this review are the mechanisms of various NP activation techniques.
