Polymeric carriers have emerged as major non-viral alternatives for gene delivery due to their lower immunogenicity and pathogenicity. However, during intracellular delivery of these carriers, multiple barriers have to be overcome or the efficiency of gene delivery will be impeded. A thorough understanding of these cellular impediments is pivotal to optimizing the efficiency of polymer-based gene delivery. This review delineates the major barriers encountered during intracellular delivery of polyplexes and discusses possible molecular designs to overcome these barriers. Based on a review of the latest strategies to enhance the intracellular delivery process, we provide insights into the further development of polymeric carriers with enhanced efficiency in transfection.
Keywords: cellular uptake; non-viral gene delivery; nucleocytoplasmic transport; polymeric vector; transfection efficiency.
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