RNA Delivery via Lipid and Polymeric Nanoparticles: Modalities, Carriers, and Therapeutic Applications-A Review

RNA therapeutics have revolutionized modern medicine by enabling precise modulation of gene expression, protein synthesis, and cellular regulation. Diverse RNA modalities including linear mRNA, circular RNA (circRNA), self amplifying RNA (saRNA), small interfering RNA (siRNA), and microRNA (miRNA) offer significant therapeutic potential in cancer therapy, vaccination, gene editing, and regenerative medicine. Despite their promise, clinical translation remains challenging due to RNA instability, rapid enzymatic degradation, negative charge, and poor membrane permeability. Consequently, the development of efficient and safe delivery systems is essential. This review comprehensively examines non viral nanocarriers designed for RNA delivery, with emphasis on lipid nanoparticles (LNPs) and polymeric systems such as poly(β amino esters) (PBAEs), PLGA, chitosan, polyethyleneimine (PEI), PAMAM dendrimers, and pABOL. Key formulation techniques including emulsion/solvent evaporation, nanoprecipitation, ionic gelation, and microfluidics are discussed in relation to nanoparticle stability, encapsulation efficiency, and scalability. Furthermore, critical biological mechanisms such as cellular uptake pathways, endosomal escape, and passive and active targeting strategies are analyzed. Collectively, advances in nanomaterial engineering and formulation technologies have established RNA nanocarriers as versatile platforms with broad applications in oncology, infectious diseases, autoimmune disorders, and regenerative medicine, paving the way toward safer and more effective clinical translation.

کلیدواژه ها:

Ribonucleic Acid (RNA) ، Polymeric nanoparticles ، Lipid nanoparticles ، Cancer Therapy ، Mechanisms