Barriers and Strategies of Cationic Liposomes for Cancer Gene Therapy

Cationic liposomes (CLs) have been regarded as the most promising gene delivery vectors for decades with the advantages of excellent biodegradability, biocompatibility, and high nucleic acid encapsulation efficiency. However, the clinical use of CLs in cancer gene therapy is limited because of many uncertain factors in vivo. Extracellular barriers such as opsonization, rapid clearance by the reticuloendothelial system and poor tumor penetration, and intracellular barriers, including endosomal/lysosomal entrapped network and restricted diffusion to the nucleus, make CLs not the ideal vector for transferring extrinsic genes in the body. However, the obstacles in achieving productive therapeutic effects of nucleic acids can be addressed by tailoring the properties of CLs, which are influenced by lipid compositions and surface modification. This review focuses on the physiological barriers of CLs against cancer gene therapy and the effects of lipid compositions on governing transfection efficiency, and it briefly discusses the impacts of particle size, membrane charge density, and surface modification on the fate of CLs in vivo, which may provide guidance for their preclinical studies. [Display omitted] The concept of lipoplexes applied to cancer gene therapy has been popular for decades; however, no such medicine has been marketed. Deng and colleagues highlight the physiological barriers against the clinical success of the cationic liposomal gene delivery system in cancer therapy. They suggest that the rational design of clinically applicable lipoplexes requires designers to pay close attention to the barriers and the impact of physicochemical properties of cationic liposomes on the therapeutic outcome.