Stimuli-responsive nitric oxide generator for light-triggered synergistic cancer photothermal/gas therapy

As a minimally invasive local cancer therapy, photothermal therapy (PTT) has aroused intensive interests in recent years. However, the therapeutic effect of PTT is still unsatisfying due to the production of heat shock proteins. Combination therapy has been regarded as a promising strategy to enhance therapeutic efficiency. In this study, a novel intelligent protoporphyrin (PpIX)-based polymer nanoplatform is developed for synergistic enhancement of cancer treatment through combined PTT and nitric oxide (NO) therapy. The core of the nanoparticle is composed of closely packed porphyrin-based NO donors and PpIX branches of the block copolymer. The prepared nanoparticles exhibit good photothermal conversion capability and high sensitivity to release NO under light illumination. And the produced high localized temperature and intracellular NO concentration could efficiently inhibit cancer cells both in vitro and in vivo. More important, this therapeutic nanoplatform can fundamentally eliminate the emergence of multidrug resistance and overcome the hypoxia microenvironment in tumors because of the absence of chemotherapeutic drugs and the oxygen-independent process, thus opening up new ideas for multifunctional therapeutic agent design for treatment of multidrug-resistant cancer.