【摘 要】
：
Although approved as an alcohol-abuse drug,disulfiram(DSF)exhibited potential anticancer activity when chelated with copper(Cu).However,the low level of intrinsic Cu,toxicity originated from exogenous Cu supplementation,and poor stability of DSF in vivo s
【机 构】
：
Biotherapy Center the First Affiliated Hospital of Zhengzhou University,Zhengzhou University,Zhengzh
论文部分内容阅读
Although approved as an alcohol-abuse drug,disulfiram(DSF)exhibited potential anticancer activity when chelated with copper(Cu).However,the low level of intrinsic Cu,toxicity originated from exogenous Cu supplementation,and poor stability of DSF in vivo severely limited its application in can-cer treatment.Herein,we proposed an in situ DSF antitumor efficacy triggered system,taking advantages of Cu-based metal-organic framework(MOF).In detail,DSF was encapsulated into Cu-MOF nanopar-ticles(NPs)during its formation,and the obtained NPs were coated with hyaluronic acid to enhance the tumor targetability and biocompatibility.Notably,DSF loaded Cu-MOF NPs maintained stability and integrity without Cu2+leakage in blood circulation,thus showing excellent biosafety.Once accumu-lating at tumor site,NPs were internalized into tumor cells via receptor-mediated endocytosis and released DSF and Cu2+simultaneously in the hyaluronidase-enriched and acidic intracellular tumor microenvironment.This profile lead to in situ chelation reaction between DSF and Cu2+,generating toxic DSF/Cu complex against tumor cells.Both in vitro and in vivo results demonstrated the programmed degradation and recombination property of Cu-based MOF NPs,which facilitated the tumor-specific chemotherapeutic effects of DSF.This system provided a promising strategy for the application of DSF in tumor therapy.
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