Stimuli-Responsive Gene Delivery Nanocarriers for Cancer Therapy

Highlights Stimuli-responsive gene delivery nanocarriers (GDNCs) possess huge potential in the gene therapy field owing to their effective protection, prolonged blood circulation, selective and targeted delivery, and controlled release of nucleic acid drugs. Recent advances in stimuli-responsive GDNCs for cancer therapy are classified, summarized, and exhibited by representative examples. The potential challenges and prospects of stimuli-responsive GDNCs toward clinical translation are outlined and the future research directions are outlooked. Gene therapy provides a promising approach in treating cancers with high efficacy and selectivity and few adverse effects. Currently, the development of functional vectors with safety and effectiveness is the intense focus for improving the delivery of nucleic acid drugs for gene therapy. For this purpose, stimuli-responsive nanocarriers displayed strong potential in improving the overall efficiencies of gene therapy and reducing adverse effects via effective protection, prolonged blood circulation, specific tumor accumulation, and controlled release profile of nucleic acid drugs. Besides, synergistic therapy could be achieved when combined with other therapeutic regimens. This review summarizes recent advances in various stimuli-responsive nanocarriers for gene delivery. Particularly, the nanocarriers responding to endogenous stimuli including pH, reactive oxygen species, glutathione, and enzyme, etc., and exogenous stimuli including light, thermo, ultrasound, magnetic field, etc., are introduced. Finally, the future challenges and prospects of stimuli-responsive gene delivery nanocarriers toward potential clinical translation are well discussed. The major objective of this review is to present the biomedical potential of stimuli-responsive gene delivery nanocarriers for cancer therapy and provide guidance for developing novel nanoplatforms that are clinically applicable.