BODIPY derivatives as light-induced free radical generators for hypoxic cancer treatment

Abstract

In photodynamic therapy, hypoxic conditions greatly impede the treatment efficacy due to the high dependence on oxygen for the generation of toxic reactive oxygen species (ROS). Accordingly, it is imperative to develop a novel oxygen-independent therapeutic strategy. Herein, the novel organic self-assembly of distyryl-diethylamine-borondipyrromethene nanoparticles (NBDP NPs) was designed to generate oxygen-independent alkyl radicals upon near-infrared light (NIR) irradiation, in which the borondipyrromethene (BODIPY) unit with a high photothermal conversion efficiency of 54% acts as an alkyl radical initiator. The experiments in vitro have proved that NBDP NPs can effectively generate alkyl radicals under hypoxic conditions and induce apoptosis. The weak acidic environment of the lysosome can further accelerate the generation of alkyl radicals. The obtained data in vivo also verify that the generated free alkyl radicals can inhibit the growth of tumor. This combination of photothermal therapy (PTT) with free radicals provides a new platform for hypoxic cancer therapy.