Generally, as 5-Fu can be transferred into cell nuclei through passive diffusion, the uptake of free 5-Fu is time prolonged and limited by the decrease of drug concentration. Therefore, identifying how to maximize the delivery and accumulation of drug in targeted nucleus is an important factor in improving its therapeutic effects. 1– 7 For some chemical nuclear-targeted drugs such as fluorouracil (5-Fu), principally used as a thymidylate synthase inhibitor for targeting the nucleus and interrupting the action of the enzyme for blocking synthesis of the pyrimidine thymidine and preventing DNA replication, 8, 9 various physiological barriers in the process must be overcome, in order to be transported into the nucleus to fulfill its antitumor effects. It is well known that the main role for a therapeutic chemical drug during tumor treatment is to overcome a series of physiological barriers and be delivered into the specific intracellular situation and induce cell apoptosis. Keywords: nucleus, nanoparticles, chitosan, protamine, cytotoxicity 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. In addition, 5-Fu-loaded chitosan–protamine NPs exhibited the best efficiency in inhibiting tumor growth than the other three formulations. 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. 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). 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. 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. Sometimes, the transportation of drugs from cytoplasm to nucleus is not efficient and often results in poor therapeutic effects. Most developed drugs are first delivered into the cytoplasm and then transferred to the nucleus through the membrane pores. Xiwei Yu, 1 Jiahui Hou, 1 Yijie Shi, 1 Chang Su, 2 Liang Zhao 1ġSchool of Pharmacy, 2School of Veterinary Medicine, Jinzhou Medical University, Jinzhou, People’s Republic of ChinaĪbstract: 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.
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