Recent Advances in Mesoporous Silica Nanoparticles Delivering siRNA for Cancer Treatment

Abstract

Silencing genes using small interfering (si) RNA is a promising strategy for treating cancer. However, the curative effect of siRNA is severely constrained by low serum stability and cell membrane permeability. Therefore, improving the delivery efficiency of siRNA for cancer treatment is a research hotspot. Recently, mesoporous silica nanoparticles (MSNs) have emerged as bright delivery vehicles for nucleic acid drugs. A comprehensive understanding of the design of MSN-based vectors is crucial for the application of siRNA in cancer therapy. We discuss several surface-functionalized MSNs’ advancements as effective siRNA delivery vehicles in this paper. The advantages of using MSNs for siRNA loading regarding considerations of different shapes, various options for surface functionalization, and customizable pore sizes are highlighted. We discuss the recent investigations into strategies that efficiently improve cellular uptake, facilitate endosomal escape, and promote cargo dissociation from the MSNs for enhanced intracellular siRNA delivery. Also, particular attention was paid to the exciting progress made by combining RNAi with other therapies to improve cancer therapeutic outcomes.

Peptide-Modified Cyclodextrin-Based Nanosystem for Co-Delivery of Celastrol and siPD-L1 to Tumors

“…14 interference (RNAi), which can inhibit the expression or transcription of specific genes. 15,16 Utilizing small interfering RNA (siRNA) targeting PD-L1 (siPD-L1) to specifically suppress the expression of PD-L1 and alter the tumor immune microenvironment is an effective immunotherapy for TNBC. However, the challenges faced by siRNA in cancer treatment include: (1) poor stability: sensitivity to endogenous nucleases and easy clearance; (2) difficulty in entry: RNA drugs, due to their negative charge and polymer properties, are difficult to enter tumor cells and exert their effects; and (3) difficulty in lysosomal escape.…”

“…Targeting PD-L1 to modulate its expression within the tumor microenvironment and initiate or enhance an antitumor immune response has emerged as a potential treatment strategy for TNBC . Meanwhile, small interfering RNA (siRNA) is a powerful tool for gene silencing through RNA interference (RNAi), which can inhibit the expression or transcription of specific genes. , Utilizing small interfering RNA (siRNA) targeting PD-L1 (siPD-L1) to specifically suppress the expression of PD-L1 and alter the tumor immune microenvironment is an effective immunotherapy for TNBC. However, the challenges faced by siRNA in cancer treatment include: (1) poor stability: sensitivity to endogenous nucleases and easy clearance; (2) difficulty in entry: RNA drugs, due to their negative charge and polymer properties, are difficult to enter tumor cells and exert their effects; and (3) difficulty in lysosomal escape. − Therefore, the design and synthesis of safe and effective siRNA delivery vectors are crucial for the development of siRNA-based therapeutics …”