College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu 610065, China.
Orthopedic Research Institution, Department of Orthopedics, West China Hospital, Sichuan University, Chengdu 610041, China.
ACS Appl Mater Interfaces. 2024 Feb 21;16(7):8484-8498. doi: 10.1021/acsami.3c18239. Epub 2024 Feb 9.
Malignant tumors are still one of the most deadly diseases that threaten human life and health. However, developing new drugs is challenging due to lengthy trials, funding constraints, and regulatory approval procedures. Consequently, researchers have devoted themselves to transforming some clinically approved old drugs into antitumor drugs with certain active ingredients, which have become an attractive alternative. Disulfiram (DSF), an antialcohol medication, can rapidly metabolize in the physiological environment into diethyldithiocarbamate (DTC) which can readily react with Cu ions in situ to form the highly toxic bis(,-diethyldithiocarbamate)-copper(II) (CuET) complex. In this study, DSF is loaded into mesoporous dopamine nanocarriers and surface-chelated with tannin and Cu to construct M-MDTC nanoprodrugs under the camouflage of K7 tumor cell membranes. After intravenous injection, M-MDTC nanoprodrugs successfully reach the tumor sites with the help of mediated cell membranes. Under slightly acidic pH and photothermal stimulation conditions, DSF and Cu are simultaneously released, forming a highly toxic CuET to kill tumor cells in situ. The generated CuET can also induce immunogenic cell death of tumor cells, increase the proportion of CD86 CD80 cells, and promote dendritic cell maturation. In vitro and in vivo studies of M-MDTC nanoprodrugs have shown excellent tumor-cell-killing ability and solid tumor suppression. This approach enables in situ amplification of chemotherapy in the tumor microenvironment, achieving an effective antitumor treatment.
恶性肿瘤仍然是威胁人类生命和健康的最致命疾病之一。然而，由于临床试验漫长、资金限制和监管审批程序，开发新的药物具有挑战性。因此，研究人员致力于将一些临床批准的旧药物转化为具有特定活性成分的抗肿瘤药物，这已成为一种有吸引力的替代方法。戒酒药双硫仑（DSF）在生理环境中可以迅速代谢为二乙基二硫代氨基甲酸盐（DTC），它可以与原位 Cu 离子迅速反应，形成高毒性的双（-二乙基二硫代氨基甲酸盐）-铜（II）（CuET）配合物。在这项研究中，DSF 被装载到介孔多巴胺纳米载体中，并与单宁和 Cu 进行表面螯合，在 K7 肿瘤细胞膜的伪装下构建 M-MDTC 纳米前药。静脉注射后，M-MDTC 纳米前药在介导的细胞膜的帮助下成功到达肿瘤部位。在略酸性 pH 和光热刺激条件下，DSF 和 Cu 同时释放，形成高毒性的 CuET 原位杀死肿瘤细胞。生成的 CuET 还可以诱导肿瘤细胞的免疫原性细胞死亡，增加 CD86 CD80 细胞的比例，并促进树突状细胞成熟。M-MDTC 纳米前药的体外和体内研究表明，它具有优异的杀伤肿瘤细胞能力和实体肿瘤抑制作用。这种方法能够在肿瘤微环境中实现原位放大化疗，实现有效的抗肿瘤治疗。
