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GNPs mediated gene delivery Schematic illustration of GNPs for the delivery of single-strand oligonucleotides including ASO, anti-miRNA, and DNAzyme.
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Single-strand oligonucleotides provide promising potential as new therapeutics towards various diseases. However, the efficient delivery of oligonucleotide therapeutics is still challenging due to their susceptibility to nuclease degradation and the lack of effective carriers for condensation. In this study, we reported the use of natural polypheno...
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Citations
... This capability extends to flavonoids, which can be effectively incorporated into nanoparticles due to their diverse pharmacological properties. One notable advantage of this approach is the potential for synergistic combinations of flavonoids with other anti-inflammatory agents [122,123]. ...
Arthritis, a global health burden comprising osteoarthritis and rheumatoid arthritis, demands advanced therapeutic approaches. In this context, flavonoids, a diverse group of naturally occurring compounds abundant in fruits, vegetables, and medicinal plants, have emerged as promising candidates for mitigating the inflammatory processes associated with arthritic conditions. This review aims, first, to provide a comprehensive exploration of the potential of flavonoids, focusing on specific compounds such as quercetin, epigallocatechin-3-gallate (EGCG), apigenin, luteolin, fisetin, silibinin, kaempferol, naringenin, and myricetin. The second section of this review delves into the anti-arthritic activities of these flavonoids, drawing insights from clinical trials and scientific studies. Each flavonoid is scrutinized individually to elucidate its mechanisms of action and therapeutic efficacy in the context of both osteoarthritis and rheumatoid arthritis. The third section of this review highlights the challenges associated with harnessing flavonoids for anti-inflammatory purposes. Bioavailability limitations pose a significant hurdle, prompting the exploration of innovative strategies such as the use of nanoparticles as delivery vehicles. In response to these challenges, the fourth section focuses on the emerging field of flavonoid-based nanoparticles. This includes detailed discussions on quercetin, EGCG, fisetin, and naringenin-based nanoparticles, highlighting formulation strategies and preclinical evidence supporting their potential in arthritis management. The targeted delivery to inflammatory sites and the exploration of synergistic combinations with other compounds are also discussed as promising avenues to enhance the therapeutic impact of flavonoids. This review consolidates current knowledge on flavonoids and their nanoformulations as potential therapeutic interventions for osteoarthritis and rheumatoid arthritis. By addressing challenges and presenting future research directions, this review aims to contribute to the advancement of innovative and effective strategies for alleviating the global burden of arthritis.
... The natural compound epigallocatechin-3-gallate (EGCG), major polyphenol in green tea, has demonstrated significant anticancer activity in both in vivo and ex vivo studies [24][25][26]. As a natural antitumor agent, EGCG inhibits tumor growth via anti-angiogenesis, inhibition of proliferation, and induction of apoptosis in tumor cells [27][28][29]. However, extensive research has revealed that EGCG suffers from issues such as instability, poor bioavailability, and a short half-life [30][31][32]. ...
Ferroptosis, a newly discovered form of regulated cell death, has garnered significant attention in the field of tumor therapy. However, the presence of overexpressed glutathione (GSH) and insufficient levels of H2O2 in the tumor microenvironment (TME) hinders the occurrence of ferroptosis. In response to these challenges, here we have constructed the self-assembled nanocomplexes (FeE NPs) utilizing epigallocatechin-3-gallate (EGCG) from green tea polyphenols and metal ions (Fe³⁺) as components. After grafting PEG, the nanocomplexes (FeE@PEG NPs) exhibit good biocompatibility and synergistically enhanced tumor-inhibitory properties. FeE@PEG NPs can be disassembled by H2O2 in the TME, leading to the rapid release of Fe³⁺ and EGCG. The released Fe³⁺ produces large amounts of toxic •OH by the Fenton reactions while having minimal impact on normal cells. The generated •OH effectively induces lipid peroxidation, which leads to ferroptosis in tumor cells. Meanwhile, the released EGCG can autoxidize to produce H2O2, which further promotes the production of •OH radicals and increases lipid peroxide levels. Moreover, EGCG also depletes the high levels of intracellular GSH, leading to an intracellular redox imbalance and triggering ferroptosis. This study provides new insights into advancing anticancer ferroptosis through rational material design, offering promising avenues for future research.
... 32 On the other hand, antisense DNA therapy is an emerging tool for several diseases including cancer. [33][34][35] This approach explores an antisense oligonucleotide as the therapeutic agent, which typically hybridizes with the complementary mRNA via Watson-Crick base pairing. This causes the downregulation of disease-causing proteins by silencing the mRNA responsible for the protein synthesis. ...
A supramolecular strategy for the design of a therapeutic nanosystem that consists of PDT active 2D nanosheets loaded with antisense DNA for the synergetic combination of PDT and antisense DNA therapy is reported.
... In this study, we used bioinformatics to predict the second structures of targeted mRNA according to minimal delta G energy. It can predict the affinity of ASO with targeted mRNA (23)(24)(25)(26)(27)(28)(29). Our team designed a new Antisense Oligonucleotide for Bcl-2 mRNA. ...
... The Lipofectamine 2000 (Invitrogen) was used in the form of a complex with the ASO based on 1:1 (w/w). The Lipofectamine (100 µg/ml) was allowed to be complexes with antisense oligonucleotides (ASO) (25,125,250,500 and 1000 nM) in serum and antibiotic-free medium before dilution and addition to cells. ...
... For better stability of this new oligo-nucleotide, we designed it to contain phosphorothionate as two wings. To enhance the cellular uptake of the designed oligonucleotide in accordance with other studies, lipofectamine nano-carrier and cationic micelle/ nisome nano-carrier were used to transport this new oligonucleotide and tamoxifen into the cells (21)(22)(23)(24)(25)(26)(27)(28)(29). ...
... These compounds, derived from diverse sources such as plants and marine organisms, exhibit multiple bioactive properties that can suppress tumor growth, induce apoptosis, inhibit angiogenesis, and modulate cellular signaling pathways involved in cancer progression [14][15][16][17][18][19][20][21][22][23][24][25][26]. To harness the full potential of natural compounds such as polyphenols, researchers have explored the use of nanoparticles (NPs) as a delivery platform for targeted and enhanced therapeutic efficacy [27][28][29][30]. NPs derived from natural compounds offer several advantages, including improved stability, solubility in biological media, controlled release of the encapsulated compounds, enhanced cellular uptake, and the ability to overcome biological barriers [30]. ...
... These reactions enable the modification of proteins and the formation of nanocomplexes with enhanced stability and triggered drug release in response to specific environmental factors. For example, polyphenols have been conjugated to proteins, such as bovine serum albumin (BSA) and RNase A via Schiff's base reactions, allowing for the controlled release of proteins in response to factors like lysosomal acidity and anionic molecules (Figure 2A) [27]. ...
Simple Summary
Conventional therapies for the treatment of colorectal cancer induce several side effects that impact the effectiveness of current therapies as well as the quality of patients’ life. In recent years, natural compounds with anticancer properties have gained attention as potential therapeutic agents for various cancers including colorectal cancer. However, several natural compounds such as polyphenols are facing obstacles for their use as anticancer drugs, such as intrinsic poor solubility, plasmatic instability, ineffective cellular uptake, and biological barriers. Currently, novel approaches in precision medicine and nanomedicine are being developed. In this context, to harness the full potential of natural compounds, researchers have explored the use of nanoparticles as a drug delivery system for targeted and enhanced therapeutic efficacy as well as limited side effects. This review provides data on recent advances in strategies using polyphenols-based nanoparticles for the treatment of colorectal cancer.
Abstract
Colorectal cancer (CRC) poses a significant challenge in healthcare, necessitating the exploration of novel therapeutic strategies. Natural compounds such as polyphenols with inherent anticancer properties have gained attention as potential therapeutic agents. This review highlights the need for novel therapeutic approaches in CRC, followed by a discussion on the synthesis of polyphenols-based nanoparticles. Various synthesis techniques, including dynamic covalent bonding, non-covalent bonding, polymerization, chemical conjugation, reduction, and metal-polyphenol networks, are explored. The mechanisms of action of these nanoparticles, encompassing passive and active targeting mechanisms, are also discussed. The review further examines the intrinsic anticancer activity of polyphenols and their enhancement through nano-based delivery systems. This section explores the natural anticancer properties of polyphenols and investigates different nano-based delivery systems, such as micelles, nanogels, liposomes, nanoemulsions, gold nanoparticles, mesoporous silica nanoparticles, and metal–organic frameworks. The review concludes by emphasizing the potential of nanoparticle-based strategies utilizing polyphenols for CRC treatment and highlights the need for future research to optimize their efficacy and safety. Overall, this review provides valuable insights into the synthesis, mechanisms of action, intrinsic anticancer activity, and enhancement of polyphenols-based nanoparticles for CRC treatment.
... Cheng et al. developed a facile, robust, and efficient strategy in delivering single-strand oligonucleotides ( Figure 3A-D) [72]. The natural polyphenol EGCG was employed to combine with oligonucleotide to prepare a negatively charged core, then ε-polylysine (PLL) (positive charge) was covered to the surface of EGCG/oligonucleotide to form the core-shell nanostructure, which was termed as green nanoparticles (GNPs). ...
Gene therapy, an effective medical intervention strategy, is increasingly employed in basic research and clinical practice for promising and unique therapeutic effects for diseases treatment, such as cardiovascular disorders, cancer, neurological pathologies, infectious diseases, and wound healing. However, naked DNA/RNA is readily hydrolyzed by nucleic acid degrading enzymes in the extracellular environment and degraded by lysosomes during intracellular physiological conditions, thus gene transfer must cross complex cellular and tissue barriers to deliver genetic materials into targeted cells and drive efficient activation or inhibition of the proteins. At present, the lack of safe, highly efficient, and non-immunogenic drug carriers is the main drawback of gene therapy. Considering the dense hydroxyl groups on the benzene rings in natural polyphenols that exert a strong affinity to various nucleic acids via hydrogen bonding and hydrophobic interactions, polyphenol-based carriers are promising anchors for gene delivery in which polyphenols serve as the primary building blocks. In this review, the recent progress in polyphenol-assisted gene delivery was summarized, which provided an easily accessible reference for the design of future polyphenol-based gene delivery vectors. Nucleic acids discussed in this review include DNA, short interfering RNAs (siRNA), microRNA (miRNA), double-strand RNA (dsRNA), and messenger RNA (mRNA).
... Polyphenols are excellent antioxidants with dense ortho and meta-phenolic hydroxyls, which can realize complexation with nucleic acids by intermolecular forces 24,25 . Recently, studies have demonstrated that polyphenols mixed with nucleic acids achieved supramolecular binding and effectively reduced the enzymatic hydrolysis risk of nucleic acids 10,26 . Therefore, to achieve effective protection of IL-10 mRNA, six frequently used polyphenols were screened. ...
... Polyphenols possess dense ortho and meta-phenolic hydroxyl groups which can complex with nucleic acids through intermolecular forces 24 . Recently, studies have revealed that small interfering RNA (siRNA) mixed with EGCG effectively reduced enzymatic hydrolysis because the polyphenolic structure enabled strong affinity to siRNA via hydrogen bonds and hydrophobic interactions 10,26 . Inspired by this, we aimed to determine the polyphenol with the strongest protective effect on mRNA by screening common polyphenols including TA, PC, EGCG, EA, CAT, and GC (Fig. 1A). ...
With the development of synthesis technology, modified messenger RNA (mRNA) has emerged as a novel category of therapeutic agents for a broad of diseases. However, effective intracellular delivery of mRNA remains challenging, especially for its sensitivity to enzymatic degradation. Here, we propose a polyphenol-assisted handy delivery strategy for efficient in vivo delivery of IL-10 mRNA. IL-10 mRNA binds to polyphenol ellagic acid through supramolecular binding to yield a negatively charged core, followed by complexing with linear polyetherimide and coating with bilirubin-modified hyaluronic acid to obtain a layer-by-layer nanostructure. The nanostructure specifically up-regulated the level of IL-10, effectively inhibited the expression of inflammatory factors, promoted mucosal repair, protected colonic epithelial cells against apoptosis, and exerted potent therapeutic efficacy in dextran sulfate sodium salt-induced acute and chronic murine model of colitis. The designed delivery system without systemic toxicity has the potential to facilitate the development of a promising platform for mRNA delivery in ulcerative colitis treatment.
... For example, it degrades rapidly by endo and exo-nucleases, misleading off-target effects and weak cellular uptake. To solve these problems, chemical modi cation of nucleotides, various modi cation on backbone or sugar rings of Deoxyribonucleotides with sulfur ion to creating phosphorothionate (PS) linkage and 2'-deoxy residues modi cations have been con rmed (14). Nanopackaging is a good way to increase cellular uptake of ASO. ...
Background
Breast cancer is a heterogenic disease and hormone dependence. Estrogen receptor is positive in more than seventy percent of breast cancer patients. Tamoxifen is an estrogen receptor (ER) antagonist and used as the first line of treatment. Drug resistance is a main reason in failure of cancer treatment and progression of the disease. Combination drug therapy is a method to treatment but is not sufficient. New approaches like molecular therapy reveal new insight to cancer therapy. Studies shown, Bcl-2 gene family inhibitors and ER blockers enhance recovery. Interfering molecules such as antisense can inhibit the expression of Bcl-2 and push the cancer cells to apoptosis. Nevertheless, their effectiveness is low, mostly due to their direct use.
Methods
Our team designed an Antisense Oligonucleotides (ASO). The MCF-7 and the MDA-MB-231breast cancer cell lines used to evaluate cellular proliferation. Liposome and cationic nano-complex (Niosome) used to increase cellular delivery of ASO and Tamoxifen. We also investigated the cytotoxicity and apoptotic effects of Tamoxifen, naked ASO and Nano-packed ASO.
Results
The ASO functional potency to assess apoptosis and expression of Bcl-2 mRNA compared in different groups. The results indicated, significant down regulation of Bcl-2 gene and inhibition of MCF-7 and MDA-MB-231 cellular proliferation. Flow-cytometry showed early apoptosis in all groups.
Conclusions
The ASO reduced the expression of Bcl-2 gene. It also had the synergistic effect with the Tamoxifen. In all studied groups, it was able to push cancer cells to apoptosis. The cationic nano-complex (Niosome) was more efficient than the liposome in delivering designed oligo antisense Bcl-2 into the cancer cells.
... Single-strand oligonucleotides and EGCG spontaneously combined to produce anionic core nanoparticles that were further coated by cationic polymers to improve their cellular internalization. The core-shell nanoparticles that were produced showed significant stability in vitro and revealed a high efficiency in the intracellular delivery of several types of nucleic acids including anti-micro ribonucleic acids (miRNA), antisense oligonucleotides, and deoxyribonucleic acid (DNA) enzymes [266]. The preparation of hydrogels by combining nucleic acids with polyphenols was also considered. ...
As naturally occurring bioactive products, several lines of evidence have shown the potential of polyphenols in the medical intervention of various diseases, including tumors, inflammatory diseases, and cardiovascular diseases. Notably, owing to the particular molecular structure, polyphenols can combine with proteins, metal ions, polymers, and nucleic acids providing better strategies for polyphenol-delivery strategies. This contributes to the inherent advantages of polyphenols as important functional components for other drug delivery strategies, e.g., protecting nanodrugs from oxidation as a protective layer, improving the physicochemical properties of carbohydrate polymer carriers, or being used to synthesize innovative functional delivery vehicles. Polyphenols have emerged as a multifaceted player in novel drug delivery systems, both as therapeutic agents delivered to intervene in disease progression and as essential components of drug carriers. Although an increasing number of studies have focused on polyphenol-based nanodrug delivery including epigallocatechin-3-gallate, curcumin, resveratrol, tannic acid, and polyphenol-related innovative preparations, these molecules are not without inherent shortcomings. The active biochemical characteristics of polyphenols constitute a prerequisite to their high-frequency use in drug delivery systems and likewise to provoke new challenges for the design and development of novel polyphenol drug delivery systems of improved efficacies. In this review, we focus on both the targeted delivery of polyphenols and the application of polyphenols as components of drug delivery carriers, and comprehensively elaborate on the application of polyphenols in new types of drug delivery systems. According to the different roles played by polyphenols in innovative drug delivery strategies, potential limitations and risks are discussed in detail including the influences on the physical and chemical properties of nanodrug delivery systems, and their influence on normal physiological functions inside the organism.
... 15−19 Cationic polymers with polyphenol have been widely used for safe and efficient gene delivery. 20 Natural polyphenols are antioxidants that have anticancer, antibacterial, and anti-inflammatory properties. 21 One of the natural polyphenols, (−)-epigallocatechin gallate (EGCG), binds to nucleic acids through hydrogen and hydrophobic interactions. ...
