mRNA delivery with templated dynamic covalent polymers

Chemical Communications, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Amphiphilic dynamic covalent polymer vectors formed in situ through RNA-templating deliver mRNA cells.

Язык: Английский

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Ionic Coating of siRNA Polyplexes with cRGD–PEG–Hyaluronic Acid To Modulate Serum Stability and In Vivo Performance

Biochemistry, Год журнала: 2025, Номер unknown

Опубликована: Март 18, 2025

Efficient delivery of siRNA-based polyplexes to tumors remains a major challenge. Nonspecific interactions in the bloodstream, limited circulation time, and nontargeted biodistribution hamper sufficient tumor accumulation. To address these challenges, we developed an ionic hyaluronic acid (HA) coating shield sequence-defined oligoaminoamide-based polyplexes. This should positive polyplex surface charge, thus reducing nonspecific enhancing serum stability. Additionally, modified HA with cyclic RGDfK (cRGD) peptide specifically target endothelial cells (TECs). Optionally, polyethylene glycol (PEG) spacer was also introduced improve ligand presentation on surface. The HA-coated exhibited favorable physicochemical properties, including negative zeta potential effective siRNA retention within polyplex, which not adversely affected by PEG or cRGD modification. In vitro analyses revealed that only enhanced cell association preserved high transfection efficiency plain cationic but coating-dependent cellular internalization, as evidenced competitive inhibition experiment. Even presence serum, encapsulated effectively, suitable particle sizes, maintained gene silencing efficiency. vivo studies involving intravenous administration into Neuro2a tumor-bearing mice showed coating, particularly when cRGD, significantly increased accumulation HA–PEG–cRGD-shielded compared Collectively, our results indicate superior performance terms stability uptake, both vivo.

Язык: Английский

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Current Development of RNA Delivery Systems

Опубликована: Янв. 1, 2025

Язык: Английский

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Investigating the Interactions of Peptide Nucleic Acids with Multicomponent Peptide Hydrogels for the Advancement of Healthcare Technologies

Gels, Год журнала: 2025, Номер 11(5), С. 367 - 367

Опубликована: Май 17, 2025

This study reports the development of peptide-based hydrogels for encapsulation and controlled release peptide nucleic acids in drug delivery applications. Ultrashort aromatic peptides, such as Fmoc-FF, self-assemble into biocompatible with nanostructured architectures. The functionalization tripeptides (Fmoc-FFK Fmoc-FFC) lysine (K) or cysteine (C) enables electrostatic covalent interactions model PNAs engineered glutamic acid residues, respectively. Hydrogels were polymerized situ presence PNAs, component ratios systematically varied to optimize mechanical properties, loading efficiency, kinetics. formulations obtained a 1/10 ratio Fmoc-FF(K C)/Fmoc-FF provided an optimal balance between structural integrity performance. All hydrogel demonstrated high stiffness (G′ > 19,000 Pa), excellent water retention, minimal swelling under physiological conditions (ΔW < 4%). studies over 10 days showed that enabled faster higher (up 90%), while bonding resulted slower, sustained (~15%). These findings highlight tunability system diverse therapeutic

Язык: Английский

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Special delivery

Nature Materials, Год журнала: 2024, Номер 23(4), С. 442 - 442

Опубликована: Апрель 1, 2024

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Amphiphilic Dynamic Covalent Polymer Vectors of siRNA

Chemical Science, Год журнала: 2024, Номер unknown

Опубликована: Дек. 30, 2024

Hydrophobization of peptide-based dynamic covalent polymer vectors boosts their siRNA delivery performances.

Язык: Английский

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Dual conjugation of magnetic nanoparticles with antibodies and siRNA for cell-specific gene silencing in vascular cells

Frontiers in Drug Delivery, Год журнала: 2024, Номер 4

Опубликована: Авг. 15, 2024

RNA therapy is a rapidly expanding field and has great promise in achieving targeted gene silencing contributing to personalized medicine. However, the delivery of molecules into organs or cells still challenging. To overcome this hurdle, number nanocarriers with pros cons have been developed. This study was designed develop simple cost-effective approach functionalize biodegradable magnetic iron nanoparticles (MNPs) for cell-specific siRNA delivery. MNPs were synthesized based on co-precipitation further functionalized sodium citrate polyethyleneimine (PEI) followed by material characterization using TEM, FTIR, Zeta potential. The PEI-coated conjugated CD31 antibody complexed linker-free approach. siRNA-loaded successfully knocked down expression GAPDH human endothelial (ECs) NOTCH3 vascular smooth muscle (VSMCs). In an EC VSMC co-culture system under shear stress mimic blood flow, specifically delivered ECs. Our represents versatile platform that could be adopted general

Язык: Английский

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Quinine-Based Polymers Are Versatile and Effective Vehicles for Intracellular pDNA, mRNA, and Cas9 Protein Delivery

Biomacromolecules, Год журнала: 2024, Номер unknown

Опубликована: Сен. 26, 2024

Quinine-based polymers have previously demonstrated promising performance in delivering pDNA cells owing to their electrostatic as well the nonelectrostatic interactions with pDNA. Herein, we evaluate whether quinine-based are versatile for delivery of mRNA and Cas9-sgRNA complexes, especially a serum-rich environment. Both complex potent therapeutics that structurally, chemically, functionally very different from By exploring family 7 vary monomer structure polymer composition, tested numerous formulations (42 pDNA, 96 mRNA, 48 Cas9-sgRNA) payload-polymer complexation compare payload-dependent structure-activity relationships. Several comparable or better than commercially available transfection agent jetPEI. The results this study demonstrate potential carrier platform wide range nucleic acid serving drug needs field genetic medicine.

Язык: Английский

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Modulating efficacy and cytotoxicity of lipoamino fatty acid nucleic acid carriers using disulfide or hydrophobic spacers

Nanoscale, Год журнала: 2024, Номер 16(29), С. 13988 - 14005

Опубликована: Янв. 1, 2024

Double pH-responsive xenopeptides comprising polar ionizable succinoyl tetraethylene pentamine (Stp) motifs and lipophilic lipoamino fatty acids (LAFs) were recently found to efficiently transfect mRNA pDNA at low doses.

Язык: Английский

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Biomimetic Nucleic Acid Drug Delivery Systems for Relieving Tumor Immunosuppressive Microenvironment

Pharmaceutics, Год журнала: 2024, Номер 16(8), С. 1028 - 1028

Опубликована: Авг. 1, 2024

Immunotherapy combats tumors by enhancing the body's immune surveillance and clearance of tumor cells. Various nucleic acid drugs can be used in immunotherapy, such as DNA expressing cytokines, mRNA vaccines, small interfering RNAs (siRNA) knocking down immunosuppressive molecules, oligonucleotides that adjuvants. Nucleic drugs, which are prone to nuclease degradation circulation find it difficult enter target cells, typically necessitate developing appropriate vectors for effective vivo delivery. Biomimetic drug delivery systems, derived from viruses, bacteria, protect cargos clearance, deliver them cells ensure safety. Moreover, they activate system through their endogenous activities active components, thereby improving efficacy antitumor immunotherapeutic drugs. In this review, biomimetic systems relieving a microenvironment introduced. Their activation mechanisms, including upregulating proinflammatory serving inhibiting checkpoints, modulating intratumoral elaborated. The advantages disadvantages, well possible directions clinical translation, summarized at last.

Язык: Английский

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