In the current era of gene delivery, trigger-responsive nanoparticles for the delivery of exogenous nucleic acids, such as plasmid DNA (pDNA), mRNA, siRNAs, and miRNAs, to cancer cells have attracted considerable interest. The cationic gene transporters commonly used are typically in the form of polyplexes, lipoplexes or mixtures of both, and their gene transfer efficiency in cancer cells depends on several factors, such as cell binding, intracellular trafficking, buffering capacity for endosomal escape, DNA unpacking, nuclear transportation, cell viability, and DNA protection against nucleases. Some of these factors influence other factors adversely, and therefore, it is of critical importance that these factors are balanced. Recently, with the advancements in contemporary tools and techniques, trigger-responsive nanoparticles with the potential to overcome their intrinsic drawbacks have been developed. This review summarizes the mechanisms and limitations of cationic gene transporters. In addition, it covers various triggers, such as light, enzymes, magnetic fields, and ultrasound (US), used to enhance the gene transfer efficiency of trigger-responsive gene transporters in cancer cells. Furthermore, the challenges associated with and future directions in developing trigger-responsive gene transporters for anticancer therapy are discussed briefly.
Keywords: anti-cancer; cationic polymer; gene delivery; glutathione; magnetic field; non-viral; photothermal; trigger-responsive; ultrasound.