High Cellular Uptake Gene Delivery Platform with Chitosan and L-arginine Complex for Cancer Treatment

Abstract

Gene therapy outperforms chemotherapy in limiting the harm to human body. A major impediment to the progress of gene therapy is a lack of proper carriers. Chitosan, derived from shellfish, is a desirable candidate for nucleic acid delivery because of its outstanding biodegradability and biocompatibility. However, previous works show that chitosan has poor cell membrane permeability. In this study, we synthesize a complex delivery system for gene therapy by compounding chitosan with L-arginine, and test the encapsulation, uptake, and cancer cell treatment power. Encapsulation efficiency of the chitosan/L-arginine complex (CA) can reach more than 90% in weight. Flow cytometry reveal that siRNA delivered by the complex can be taken in by cells 10 times better than free siRNA and 2 times better than chitosan alone. Confocal imaging confirmed the high cellular uptake, and siRNA tests in HeLa cells indicate the successful silencing of the target gene (RRM2). The complex serves as a gene delivery system that is capable of loading and delivering a variety of genetic materials in which the specific nucleic acid molecule to be delivered could be altered at will.