AND-gate fluorescence prodrug of the self-immolative delivery for overcoming multidrug resistance

Abstract

The principle goal of clinical tumor treatment is to improve the therapeutic outcomes in the clinic while suppressing undesired purgatorial side-effects of anticancer drugs. However, its clinical usage of fluorescence prodrug was significantly hampered with some critical issues such as water-solubility, blood circulation, therapeutic efficacy, inevitable leakage, and side effects simultaneously. Herein, based on the strategy of the unique grafting structure, we report H2O2 activatable phototheranostic probes targeting the Golgi in drug-induced kidney injury tissues of mice with hypertension. The drug release study in vitro demonstrated that LGM-XL can diagnose cancer effectively by monitoring fluctuations of H2O2 in vivo through fluorescence imaging. More importantly, the prodrug LGM-XL could detect and image endogenous H2O2 in inflamed mice in situ, while effectively avoiding drug leakage in blood. The novel multifunctional drug delivery system enhanced not only Golgi oxidative stress in the pathophysiology of hypertension by stimulation of H2O2 but also the molecular mechanism for the diagnosis of inflamed-related diseases (e.g., drug-induced liver injury and the liver repair).