Nano/micro-scale targeted RNA delivery systems for cancer therapy

RNA therapy has emerged as a transformative approach for treating cancer. However, the clinical application of RNA therapy faces significant challenges due to the biological barriers such as enzymatic degradation, reticuloendothelial system (RES) clearance, and low transfection efficiency. To address these limitations, a huge number of engineered nano/micro-scale vehicles have been thoroughly investigated and extensively used for targeted delivery of RNA. In this work, we summarized a comprehensive review of the nano/micro-scale targeted RNA delivery systems, coupled with critical insights into challenges and opportunities. We firstly reviewed the various nano/micro-scale vectors and technologies for RNA delivery in cancer therapy, including lipid nanoparticles, polymeric micelles, hydrogels, microneedles, exosomes, nanoparticles, metal-organic framework, covalent organic frameworks and living cells. We further summarized the challenges, highlighting the potential to achieve high therapeutic efficacy and minimal side effects. Ultimately, the perspectives of nano/micro-scale targeted RNA delivery systems are thoroughly discussed. Collectively, we believe that RNA therapies based on nano/micro-scale delivery strategies could be potentially applied in clinical fields to promote the improvement of cancer treatments.