期刊
ACS APPLIED MATERIALS & INTERFACES
卷 13, 期 31, 页码 36894-36908出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsami.1c09346
关键词
nanocrystals; drug delivery; cupric diethyldithiocarbamate; fucoidan; selectin; tumor microenvironment
资金
- National Natural Science Foundation of China [81803439]
- Youth Foundation of Jiangsu Province [BK20180699]
The study demonstrated that utilizing P-selectin as a target for drug nanocrystals to tumors can enhance drug accumulation and anti-tumor efficacy, while maintaining a good safety profile for cancer treatment.
The vascular wall is the first physiologic barrier that circulating nanoparticles (NPs) encounter, which also is a key biological barrier to cancer drug delivery. NPs can continually scavenge the endothelium for biomarkers of cancer, and the chance of NPs' extravasation into the tumors can be enhanced. Here, we envision P-selectin as a target for specific delivery of drug nanocrystals to tumors. The cupric diethyldithiocarbamate nanocrystals (CuET NCs) were first prepared by an antisolvent method, and then nanocrystals were coated with fucoidan via physical interaction. The fucoidan-coated CuET nanocrystals (CuET@Fuc) possess high drug loading and have the ability to interact with human umbilical vein endothelial cells expressing P-selectin, which transiently enhances the endothelial permeability and facilitates CuET@Fuc extravasation from the peritumoral vascular to achieve higher tumor accumulation of drugs than bare CuET NCs. The CuET NC shows poorer anticancer efficacy than CuET@Fuc at the same dose of CuET. Upon repeated dosing of CuET@Fuc for 2 weeks, no mortality was observed in treated melanoma-bearing mice, while the mortality in the control group and excipient-treated groups reached 23%. The growth rate of melanoma in the CuET@Fuc-treated group was significantly lower than those in other groups. Furthermore, an acute toxicity study revealed that CuET@Fuc is a safe formulation for cancer treatment.
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