摘要
The H_(2)O_(2) -triggered prodrug activation represents a hot topic while the low H_(2)O_(2) level of cancer cells hindered the complete activation of parent drugs and resulted in the poor therapeutic effect. Here, we developed an H_(2)O_(2) amplifier fabricated by crosslinked lipoic acid nanocapsules(cLANCs), which would selectively elevate the intracellular H_(2)O_(2) level of cancer cells 3.4-fold higher than that of untreated cancer cells so as to speed up the activation of parent drug from the loaded prodrugs(Pro-5-FU). The cytotoxicity showed that the killing effect of Pro-5-FU loaded in cLANCs(Pro-5-FU@cLANCs) arrived up to 1.6-time higher than that of Pro-5-FU alone against A549 cells, and was even close to free 5-FU. The in vivo anticancer evaluation gave the tumor inhibition rate(TIR) and survival rate(SR) of Pro-5-FU@cLANCs against A549 tumor-bearing nude mice up to 73.1% and 80%,respectively, much higher than those of Pro-5-FU(TIR: 41.2%, SR: 20%) or free 5-FU(TIR: 50.6%, SR: 0%). This nanodrug constructed the first example that utilizes the drug carriers as H_(2)O_(2) amplifier to strengthen the prodrug activation.
基金
supported by the National Natural Science Foundation of China (22201193 and 21975165)
the Innovative Research Team Program of Sichuan Province (2021JDTD0015)
the National Natural Science Foundation of Sichuan Province (2023NSFSC1691)。
