Rational design of siRNA-based delivery systems for effective treatment of brain diseases

Abstract

Effective clinical methods are urgently required to treat brain diseases. Small interfering RNAs (siRNAs) are promising in the treatment of brain diseases because of their ability to target and specifically silence genes associated with disease progression. However, their effectiveness is hindered by physiological barriers such as enzymatic degradation, the blood-brain barrier, and the blood-brain tumor barrier, severely restricting them from reaching the desired target sites. The development of nanotechnology has made the effective delivery of siRNAs to the brain possible. This is accomplished by encapsulating siRNAs in cationic polymers, liposomes, or micelles to improve their stability and targeting efficiency. In this review, we first analyzed the limitations of siRNA delivery in brain diseases such as brain tumors, stroke, and neurodegenerative diseases. Next, we summarized how nanotechnology can offer a solution by enabling effective siRNA delivery to the brain and improving the intracellular transfection efficiency of siRNA. Finally, we discussed the challenges and future advances of siRNA-based delivery systems to facilitate their clinical translation. This review emphasizes the importance of overcoming physiological barriers associated with siRNA delivery and highlights recent advances in the rational design of siRNA-based delivery systems for the effective treatment of brain diseases.