In this study, we attempted to elucidate the capability of a natural polymer dextran, by modification with histidine, to be an efficient, safe and promising nucleic acid delivery system in gene therapy. Physicochemical characterizations were performed to get an insight into the derivative. The efficiency of the derivative as a gene delivery vehicle was also studied in depth using fluorescence microscopy. Extensive efforts were made to have a better understanding of the cellular dynamics involved. The derivative proved itself to be 6.7-fold more excelling than PEI in its transfecting capability. Mechanisms underlying cellular internalization, vector unpacking, intranuclear localization and transgene expression were also investigated. The possibility of recruiting intracellular histone to promote the entry of the gene into the nucleus seemed promising. Our findings also explored the links that mediate the correlation between the uptake of the derivative and various endocytic pathways. The results thus obtained reflect the success of the entire journey of the synthesized delivery vehicle.
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