Mitochondria-Targeting Thermosensitive Initiator with Enhanced Anticancer Efficiency

As one of the most important organelles in cells, the mitochondrion has been reported to exhibit higher temperatures and is vulnerable to free radicals, especially in cancer cells. Here, we report on the use of a mitochondria-targeted thermosensitive radical initiator for cancer cell killing. The thermal-sensitive radical initiator, V044 (2,2'-azobis [2-(2-imidazolin-2-yl)propane]dihydrochloride), was applied as a radical source, which was linked with a mitochondrial targeting moiety, triphenylphosphine (TPP), to construct the mitochondria-targeting radical initiator (TPPV). Mitochondria were applied as the endogenous thermal source of cells, which accelerated the free radical generation of TPPV. Results showed that TPPV could effectively generate free radicals in the mitochondrial area, and the released free radicals effectively damaged mitochondria, exhibiting an enhanced anticancer efficiency. This therapy based on endogenous mitochondrial heat avoids tissue penetration limits and offers a target for mitochondria-targeting systems.