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RNA interference (RNAi) is an endogenous post-transcriptional gene regulatory mechanism, where non-coding, double-stranded RNA molecules interfere with the expression of certain genes in order to silence it. Since its discovery, this phenomenon has evolved as powerful technology to diagnose and treat diseases at cellular and molecular levels. With...
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RNA interference (RNAi) with small interfering RNA (siRNA) is expected to offer an attractive means to specifically and efficiently silence disease-associated genes for treating various diseases provided that safe and efficient delivery systems are available. In this study, we have established an arginine-decorated amphiphilic dendrimer composed of...
Citations
... Researchers have also attempted to leverage circRNA stability to guide the generation of chimeric antigen receptor (CAR) T cells by introducing CAR-expressing circRNA into T cells to avoid the time-consuming approach of producing CAR-T cells via T cell separation followed by engineering [68]. The use of nanoparticles as a delivery vehicle has considerably increased the in vivo efficiency of circRNA-based therapies [69]. ...
... Using endogenous or exogenous ligands, a siRNA delivery method mediated by lipid nanoparticles (LNPs) targets circRNAs in the cytoplasm of particular cells. Because nanoparticles cannot penetrate the nucleus, this method can only target circRNAs in the cytoplasm [69]. Using lentiviral and adenoviral circRNA expression plasmids, circRNA vectors are overexpressed in vivo [71]. ...
Biotechnology is one of the emerging fields that can add new and better application in a wide range of sectors like health care, service sector, agriculture, and processing industry to name some. This book will provide an excellent opportunity to focus on recent developments in the frontier areas of Biotechnology and establish new collaborations in these areas. The book will highlight multidisciplinary perspectives to interested biotechnologists, microbiologists, pharmaceutical experts, bioprocess engineers, agronomists, medical professionals, sustainability researchers and academicians. This technical publication will provide a platform for potential knowledge exhibition on recent trends, theories and practices in the field of Biotechnology
... The tuneable properties of AuNPs enable them to manifest in various morphologies, significantly enhancing their sensitivity for surface-enhanced Raman scattering (SERS), a crucial aspect for precise cancer imaging and detection [38]. In addition, AuNPs are recognized for their high chemical stability and low toxicity compared with other nanoparticle types [39,40]. These favourable characteristics position AuNPs as promising candidates for various biomedical applications. ...
... siRNAs, designed to selectively switch off specific cancer genes, are becoming integral to this rapidly advancing domain. To achieve this, siRNAs can be (i) directly conjugated to the AuNP surface via a gold-thiol bond or electrostatic interaction, and (ii) adhered to the AuNP surface modified with a polymer layer [40]. ...
Objectives
In recent years, theranostic applications have emerged as promising tools in the fight against lung and breast cancers. This review aims to provide an in-depth exploration of the proof-of-concept theranostic applications of two cutting-edge nanomaterials: gold nanoparticles (AuNPs) and graphene.
Key findings
Nanotechnology plays a revolutionary role in cancer theranostics. AuNPs’ properties include high surface plasmon resonances, advantageous surface-to-volume ratio, remarkable photothermal conversion rates, and distinctive optical characteristics. Whereas graphene boasts high surface areas, optical transparency, and remarkable versatility in surface functionalization. While AuNPs have long been recognized for their theranostic potential, this review spotlights the burgeoning role of graphene as a compelling choice for advancing theranostic applications in oncology with several exemplary studies. In fact, most recent advancements have witnessed the integration of AuNP-graphene nanocomposites in theranostic approaches targeting lung and breast cancers. Yet, there are still many intricate challenges that researchers face in harnessing the full potential of these nanomaterials in theranostics, from synthesis to clinical translation.
Summary
This review provides valuable insights into both established and emerging nanomaterials. AuNPs show significant potential for diverse cancer theranostic applications, and graphene is rapidly evolving as a next-generation theranostic platform. The hybrid AuNP-graphene nanocomposite stands out as a promising candidate in the evolving landscape of cancer therapy, offering exciting prospects for future research and development.
... Composite nanomaterials have high stability in biological fluids, and they also have features such as biodegradability, renewability, and biocompatibility [14,15]. The fact that these properties can be improved makes composite materials suitable for use in agriculture, energy, cosmetics, etc., and enables its use in various sectors including pharmaceuticals, food safety, and preservation [16,17]. ...
In this study, CaO-Fe and CaO-Ag nanocomposites were synthesized and various biological properties were characterized. E. coli cell viability, antimicrobial, antioxidant, antibiofilm, and DNA cleavage properties were examined. All nanocomposites, namely raw CaO-Ag (R-CaO-Ag), hydrolyzed CaO-Ag (H-CaO-Ag), raw CaO-Fe (R-CaO-Fe), and hydrolyzed CaO-Fe (H-CaO-Fe), were found to have good antioxidant, antimicrobial, and antibiofilm properties. They showed antioxidant activity of 83.33%, 70.60%, 74.73%, and 72.78%, respectively, at 200 mg/L nanocomposites. When DNA cleavage properties of R-CaO-Ag, H-CaO-Ag, R-CaO-Fe, and H-CaO-Fe were evaluated at different concentrations, single-strand break was observed for all samples. It was shown that R-CaO-Ag was more effective against S. aureus and C. tropicalis, and H-CaO-Ag was more effective against E. hirae. It was found that the antimicrobial activities of R-CaO-Ag and H-CaO-Ag were higher compared to R-CaO-Fe and H-CaO-Fe. The microbial cell viability of nanocomposites was examined at three different concentrations. Even at the lowest concentration (125 mg/L), high values of E. coli inhibition were found as 98.65%, 100%, 90.24%, and 88.63%, respectively. Also, it was observed that all nanocomposites exhibited excellent biofilm inhibition activities. The antibiofilm abilities of one Gr (+) and one Gr (−) microorganism at three different concentrations were investigated. Biofilm inhibition percentages of R-CaO-Ag, H-CaO-Ag, R-CaO-Fe, and H-CaO-Fe were found as 65.83%, 86.5%, 89.67%, and 93.62% for S. aureus at 500 mg/L, respectively, while it was 50.06%, 90.68%, 71.69%, and 92.36% for P. aeruginosa, respectively, at 500 mg/L.
... In the acidic environment of endosomes, the amino groups are protonated and their positive charge promotes interaction with anionic endosome lipids, inducing destabilization of the endosome membrane and promoting the release of mRNA into the cytosol (Wan et al., 2014;Draz et al., 2014;Tam et al., 2013), as also briefly mentioned in the aforementioned EMA report: ...
The medicinal preparation called Comirnaty by Pfizer-BioNTech is an aqueous dispersion of lipid nanomaterials, intended to constitute, after thawing and dilution, the finished product for intramuscular injection. In the present study, we examine some evident chemical-physical criticalities of the preparation, particularly regarding the apparent and the intrinsic pKa (acid dissociation constant) of its main excipient, the ionizable cationic lipid ALC-0315. The very high value of its intrinsic pKa causes, after internalization and endosomal escape of LNPs, a sudden increase of its cationic charge concentration and consequently the formation of pro-inflammatory cytokines and ROS (reactive oxygen species), that can disrupt the mitochondrial membrane and release its content, cause RNA mistranslation, polymerization of proteins and DNA, DNA mutations, destruction of the nuclear membrane and consequent release of its content. Additionally, the apparently low pKa value (6.09) of ALC-0315 associated with other lipids in the LNP, is not suitable for intramuscular application. Its value is too low to enable a proper transfection of host cells, despite what is stated by EMA (European Medicines Agency) in its Assessment report dated 19 February 2021, in flagrant contradiction with the same bibliographic source therein cited. Furthermore, the exceptional penetrability, mobility, chemical reactivity and systemic accumulation of uncontrollable cationic lipid nanoparticles, with high cytotoxicity levels, shed in unpredictable biological locations, even far from the site of inoculation, are all factors that can lead to an unprecedented medical disaster. Meanwhile, further immediate studies and verifications are recommended, taking into consideration, in accordance with the precautionary principle, the immediate suspension of vaccinations with the COVID-19 mRNA- LNP-based vaccines.
... These limitations can hinder cellular uptake and tissue penetration of siRNAs, ultimately compromising their therapeutic effectiveness. Furthermore, the RNA backbone contains ribose, which is highly susceptible to hydrolysis by serum nucleases that cleave phosphodiester bonds [65,66]. This degradation process prevents the accumulation of intact therapeutic siRNA in targeted tissue after systemic administration [39]. ...
... Throughout this journey, siRNAs must resist nuclease degradation to retain functionality [78]. Using siRNA delivery vehicles to protect against degradation in the circulatory system is critical for practical siRNA-mediated silencing [66]. Nanocarriers can be designed to shield siRNA from ribonucleases, ensuring stability and resistance to enzymatic degradation. ...
RNA has emerged as a revolutionary and important tool in the battle against emerging infectious diseases, with roles extending beyond its applications in vaccines, in which it is used in the response to the COVID-19 pandemic. Since their development in the 1990s, RNA interference (RNAi) therapeutics have demonstrated potential in reducing the expression of disease-associated genes. Nucleic acid-based therapeutics, including RNAi therapies, that degrade viral genomes and rapidly adapt to viral mutations, have emerged as alternative treatments. RNAi is a robust technique frequently employed to selectively suppress gene expression in a sequence-specific manner. The swift adaptability of nucleic acid-based therapeutics such as RNAi therapies endows them with a significant advantage over other antiviral medications. For example, small interfering RNAs (siRNAs) are produced on the basis of sequence complementarity to target and degrade viral RNA, a novel approach to combat viral infections. The precision of siRNAs in targeting and degrading viral RNA has led to the development of siRNA-based treatments for diverse diseases. However, despite the promising therapeutic benefits of siRNAs, several problems, including impaired long-term protein expression, siRNA instability, off-target effects, immunological responses, and drug resistance, have been considerable obstacles to the use of siRNA-based antiviral therapies. This review provides an encompassing summary of the siRNA-based therapeutic approaches against viruses while also addressing the obstacles that need to be overcome for their effective application. Furthermore, we present potential solutions to mitigate major challenges.
... Notwithstanding the prevailing optimism, there exist apprehensions. The potential hazard of cytotoxicity is a significant limitation, particularly in the case of metal-based nanoparticles, as they may cause cytotoxicity by discharging ion fragments or reactive oxygen species, which could compromise the safety of therapeutic interventions [49]. ...
Advancements in the clinical applications of small interfering RNA (siRNA) in cancer therapy have opened up new possibilities for precision medicine. siRNAs, as powerful genetic tools, have shown potential in targeting and suppressing the expression of specific genes associated with cancer progression. Their effectiveness has been further enhanced by incorporating them into nanoparticles, which protect siRNAs from degradation and enable targeted delivery. However, despite these promising developments, several challenges persist in the clinical translation of siRNA-based cancer therapy. This comprehensive review explores the progress and challenges associated with the clinical applications of siRNA in cancer therapy. This review highlights the use of siRNA-loaded nanoparticles as an effective delivery system for optimizing siRNA efficacy in various types of carcinomas and the potential of siRNA-based therapy as a genetic approach to overcome limitations associated with conventional chemotherapeutic agents, including severe drug toxicities and organ damage. Moreover, it emphasizes on the key challenges, including off-target effects, enzymatic degradation of siRNAs in serum, low tumor localization, stability issues, and rapid clearance from circulation that need to be addressed for successful clinical development of siRNA-based cancer therapy. Despite these challenges, the review identifies significant avenues for advancing siRNA technology from the laboratory to clinical settings. The ongoing progress in siRNA-loaded nanoparticles for cancer treatment demonstrates potential antitumor activities and safety profiles. By understanding the current state of siRNA-based therapy and addressing the existing challenges, we aim to pave the way for translating siRNA technology into effective oncologic clinics as an improved treatment options for cancer patients.
... Additionally, to investigate the relationships between circRNAs and OSCC, the overexpression/inhibition of circRNAs is the main method used to explore their functional implications. Some approaches can be used to overexpress or knockdown circRNAs, including: the CRISPR/Cas9mediated circRNA knockout strategy [40]; using short interfering RNAs (siRNAs) to induce the circRNA cleavage strategy [41]; the CRISPR/Cas13-mediated circRNA knockdown strategy [42]; and the circRNA expression plasmid strategy [43]. Moreover, RNase R can be used to verify the circular structure of circRNAs. ...
CircRNAs are a class of endogenous long non-coding RNAs with a single-stranded circular structure. Most circRNAs are relatively stable, highly conserved, and specifically expressed in tissue during the cell and developmental stages. Many circRNAs have been discovered in OSCC. OSCC is one of the most severe and frequent forms of head and neck cancer today, with a poor prognosis and low overall survival rate. Due to its prevalence, OSCC is a global health concern, characterized by genetic and epigenomic changes. However, the mechanism remains vague. With the advancement of biotechnology, a large number of circRNAs have been discovered in mammalian cells. CircRNAs are dysregulated in OSCC tissues and thus associated with the clinicopathological characteristics and prognosis of OSCC patients. Research studies have demonstrated that circRNAs can serve as biomarkers for OSCC diagnosis and treatment. Here, we summarized the properties, functions, and biogenesis of circRNAs, focusing on the progress of current research on circRNAs in OSCC.
... Positively charged polymers (ie, poly-L-lysine, PLL) can electrostatically attach to the surface of sulfur-enriched Bi 2 S 3 QDs (PLL-Bi 2 S 3 QDs) for enhancing cellular uptake/penetration. 222 The QDs have good colloidal stability in cell culture medium after 7 days, with size approximately 10 to 12 nm, and zeta potential approximately 20 mV. The absorption spectrum for PLL-Bi 2 S 3 QDs showed that the particles absorb visible and NIR light ( Figure 8A). ...
Theranostic agents are promising due to their ability to diagnose, treat and monitor different types of cancer using a variety of imaging modalities. The advantage specifically of nanoparticles is that they can accumulate easily at the tumor site due to the large gaps in blood vessels near tumors. Such high concentration of theranostic agents at the target site can lead to enhancement in both imaging and therapy. This article provides an overview of nanoparticles that have been used for cancer theranostics, and the different imaging, treatment options and signaling pathways that are important when using nanoparticles for cancer theranostics. In particular, nanoparticles made of metal elements are emphasized due to their wide applications in cancer theranostics. One important aspect discussed is the ability to combine different types of metals in one nanoplatform for use as multimodal imaging and therapeutic agents for cancer.
... 134 Being positively charged the polymeric complex enables endosomal release due to proton sponge effects, thus improving the siRNA's cellular uptake. 135 In addition to positively charged functional groups that usually bind to siRNA, hydrophobic polymers are also efficacious for siRNA delivery. 136,137 The hydrophobic molecules such as cholesterol conjugation to siRNA with an optimal balance of pK a between 6.0 and 6.5 are implicated in effective siRNA delivery. ...
Small molecule, peptide, and protein-based drugs have been developed over decades to treat various diseases. The importance of gene therapy as an alternative to traditional drugs has increased after the discovery of gene-based drugs such as Gendicine for cancer and Neovasculgen for peripheral artery disease. Since then, the pharma sector is focusing on developing gene-based drugs for various diseases. After the discovery of the RNA interference (RNAi) mechanism, the development of siRNA-based gene therapy has been accelerated immensely. siRNA-based treatment for hereditary transthyretin-mediated amyloidosis (hATTR) using Onpattro and acute hepatic porphyria (AHP) by Givlaari and three more FDA-approved siRNA drugs has set up a milestone and further improved the confidence for the development of gene therapeutics for a spectrum of diseases. siRNA-based gene drugs have more advantages over other gene therapies and are under study to treat different types of diseases such as viral infections, cardiovascular diseases, cancer, and many more. However, there are a few bottlenecks to realizing the full potential of siRNA-based gene therapy. They include chemical instability, nontargeted biodistribution, undesirable innate immune responses, and off-target effects. This review provides a comprehensive view of siRNA-based gene drugs: challenges associated with siRNA delivery, their potential, and future prospects.
... Risk factors include genetics, smoking, history of cancer treatment, chemical exposure and family history [320]. Traditional DDSs used for treating leukemia revealed some challenges such as stability, drug leakage and toxicity [321][322][323][324]. ...
A wide range of nanomaterials has been developed for biomedical applications, such as drug delivery for cancer treatment. These include nanoparticles and nanofibers with various dimensions that are both natural and synthetic. A successful drug delivery system (DDS) is characterized by its biocompatibility, intrinsic high surface area, high interconnected porosity and chemical functionality. These features have been recently achieved with the most recent advances in the development of metal–organic framework (MOF) nanostructures. MOFs are assemblies of metal ions and organic linkers that are made in different geometries and can be produced in 0, 1, 2 or 3 dimensions. MOFs are characterized by their outstanding surface area, interconnected porosity as well as the variable chemical functionality. These characteristics provide unlimited modalities for the loading of drugs into their hierarchical structures. Combined with biocompatibility pre-requisites, MOFs are now considered among the most successful DDS for the treatment of various diseases; hence, the term “BioMOF” has been used to refer to MOFs with potential for biomedical applications. This review outlines the development and applications of DDS based on pristine and chemically functionalized BioMOF nanostructures for the treatment of cancer. A brief description of the structure, synthesis and mode of action of BioMOF DDS systems is provided.
