Research and application progress of siRNA nano-delivery systems in gliomas

Gliomas are the most common and highly harmful primary central nervous system tumors. Small interfering RNA (siRNA) has been proposed as a promising therapeutic strategy for glioma by specifically silencing target gene expression. However, the instability of siRNA and its poor permeability across the blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB) have significantly limited its clinical application. Therefore, appropriate delivery systems are urgently required to enhance the stability and targeting efficiency of siRNA. Nano-delivery systems, due to advantages such as protecting siRNA from being degraded by enzymes, increasing the rate of drug entry into the brain, and enabling targeted delivery, have become an effective means to solve the problem of siRNA treatment for glioma. This review outlines the design strategies, types, and application progress of siRNA nano-delivery systems for glioma treatment. It focuses on how biological macromolecule-based, polymer-based, lipid-based, inorganic, and biomimetic systems overcome in vivo delivery barriers through their material properties and functional modifications. The review also covers the mechanisms by which siRNA inhibits glioma, the strategies carriers use to cross the BBB, and combination therapy approaches. It then discusses the current challenges in this field and the prospects for clinical translation.