Cucurbit[8]uril-based supramolecular polymer nanocapsules as an effective siRNA delivery platform for gene therapy

Abstract

Short interfering ribonucleic acid (siRNA) therapeutics show great promise for cancer therapy by gene-specific suppression. Developing a safe and effective siRNA delivery platform remains one key challenge for their clinical applications. Here, a novel type of supramolecular polymer nanocapsule (NC) has been constructed by co-assembly of cucurbit[8]uril (CB[8]) and a triviologen derivative for siRNA delivery to inhibit target gene expression. The nanocapsules with a positively charged surface can absorb siRNA to form a NCs-siRNA complex with high loading capacity and then release it in an acidic microenvironment. What's more, gel retardation electrophoresis experiments, confocal microscopy analysis and cell viability assay have demonstrated that the nanocapsules are able to protect the siRNA from enzymatic degradation and have exhibited advantages for intracellular siRNA delivery such as high cellular uptake and low cytotoxicity. More importantly, western blotting methods and flow cytometry analysis have shown that the NCs-siRNA complex exhibited efficient protein expression suppression and apoptosis-induced efficacy. Our results suggest that the constructed supramolecular polymer nanocapsules could be an effective siRNA carrier for gene therapy.