Nanoparticles Used for the Delivery of RNAi-Based Therapeutics

作者：Tianrui Ren, Liang Ma, Ping Fu, Chuyue Zhang · 发表于：Pharmaceutics · 年份：2025 · DOI：10.3390/pharmaceutics17111502 · 被引用次数：17 · 研究领域：RNA Interference and Gene Delivery、Extracellular vesicles in disease、Nanoplatforms for cancer theranostics

RNA interference (RNAi) offers programmable, sequence-specific silencing via small interfering RNA (siRNA) and microRNA (miRNA), but clinical translation hinges on overcoming instability, immunogenicity, and inefficient endosomal escape. This review synthesizes advances in non-viral nanocarriers-liposomes, polymeric nanoparticles, and extracellular vesicles (EVs)-that stabilize nucleic acids, tune biodistribution, and enable organ- and cell-selective delivery. We highlight design levers that now define the field: ligand-guided targeting, stimuli-responsive release, biomimicry and endogenous carriers, and rational co-delivery with small molecules. Across major disease areas-cancer and cardiovascular, respiratory, and urological disorders-these platforms achieve tissue-selective uptake (e.g., macrophages, endothelium, and myocardium), traverse physiological barriers (including the blood-brain barrier and fibrotic stroma), and remodel hostile microenvironments or immune programs to enhance efficacy while maintaining favorable safety profiles. Early clinical studies reflect this diversity, spanning targeted nanoparticles, local drug depots, exosome and cellular carriers, and inhaled formulations, e.g., and converge on core phase-I endpoints (safety, maximum tolerated dose, pharmacokinetics/pharmacodynamics, and early activity). Looking ahead, priorities include good manufacturing practice scale, consistent manufacture-especially for EVs; more efficient loading and cargo control; ...