Abstract
Anticancer platinum prodrugs that can be controllably activated are highly desired for personalized precision medicine and patient compliance in cancer therapy.However,the clinical application of plat-inum(Ⅳ)prodrugs(Pt(Ⅳ))is restricted by tissue penetration of external irradiation.Here,we report a novel Pt(Ⅳ)activation strategy based on endogenous luminescence of tumor microenvironment respon-siveness,which completely circumvents the limitation of external irradiation.The designed Pt(Ⅳ)-Lu,a mixture of trans,trans,trans-[Pt(N3)2(OH)2(py)2]and luminol(Lu),has controllable activation property:it remains inert in reductant environment and normal tissues,but under tumor microenvironment,Lu will be oxidized to produce blue luminescence,which rapidly reduce Pt(Ⅳ)to Pt(Ⅱ)without the need of any external activator.Pt(Ⅳ)-Lu shows excellent responsive antitumor ability both in vitro and in vivo.Compared to cisplatin,the median lethal dose in BALB/c mice increased by an order of magnitude.Our results suggest that Pt(Ⅳ)-Lu exhibits highly controllable activation property,superior antitumor activity,and good biosafety,which may provide a novel strategy for the design of platinum prodrugs.
基金项目
National Natural Science Foundation of China(32201171)
National Natural Science Foundation of China(82372115)
Science and Technology Program of Guangzhou(202102021266)
维普
万方数据