Near-infrared light triggered photothermal and photodynamic therapy with an oxygen-shuttle endoperoxide of anthracene against tumor hypoxia

Abstract

Hypoxia, defined as an oxygen-deficient condition, is known to be a characteristic feature for most solid tumors that not only facilitates tumor metastasis but also jeopardizes the efficacy of therapies, especially photodynamic therapy (PDT) in which oxygen is essential in the treatment process. To overcome this problem, novel oxygen self-carrying nanoparticles (PMT NPs) have been developed for highly efficient and selective cancer treatment. Substituted diphenyl anthracene is designed as a more suitable ¹O₂ donor compared to diphenyl anthracene. Photooxidation in situ of diphenyl anthracene is achieved by introducing tetraphenyl porphyrin (TPP) into the polymer architecture. Micelles are obtained by a nanoprecipitation method and IR780 is encapsulated into the core of the micelles as a photosensitizer. Once the PMT NPs are ingested by HepG2 cells, they can induce the release of reactive oxygen species (ROS) to kill cancer cells with 808 nm laser irradiation. The micelles are about 60 nm in diameter with a narrow distribution, and are quite suitable for passive targeting to tumors via the enhanced permeability and retention (EPR) effect. In the presence of an 808 nm laser, the PMT NPs can release ROS and in turn significantly enhance the PDT effect. This innovative nanoplatform has exhibited excellent antitumor efficiency, was clearly verified by in vitro and in vivo assays, and may serve as a versatile theranostic platform for clinical tumor therapy.