Preparation and characterization of novel chitosan–protamine nanoparticles for nucleus-targeted anticancer drug delivery

It is well known that most anticancer drugs commonly show high toxicity to the DNA of tumor cells and exert effects by combining with the DNA or associated enzymes in the nucleus. Most developed drugs are first delivered into the cytoplasm and then transferred to the nucleus through the membrane pores. Sometimes, the transportation of drugs from cytoplasm to nucleus is not efficient and often results in poor therapeutic effects. In this study, we developed special and novel nanoparticles (NPs) made of chitosan and protamine for targeted nuclear capture of drugs to enhance anticancer effects. The anticancer effects of nuclear targeted-delivery of drugs in NPs were also evaluated by investigating cytotoxicity, cellular uptake mechanism, and cell apoptosis on cells. Chitosan–protamine NPs were characterized by good drug entrapment, sustained release, small average particle size, low polydispersity index, and high encapsulation efficiency; and accomplished the efficient nuclear delivery of fluorouracil (5-Fu). Compared with free 5-Fu and 5-Fu-loaded chitosan NPs, treatment of A549 cells and HeLa cells with 5-Fu-loaded chitosan–protamine NPs showed the highest cytotoxicity and further induced the significant apoptosis of cells. In addition, 5-Fu-loaded chitosan–protamine NPs exhibited the best efficiency in inhibiting tumor growth than the other three formulations. 5-Fu-loaded chitosan–protamine NPs enhanced antitumor efficacy through the targeted nuclear capture of drugs and showed promising potential as a nanodelivery system for quickly locating drugs in the nucleus of cells.