Light-Activated Hypoxia-Responsive Nanoparticles for Photodynamic Chemotherapy

Hypoxia is a characteristic of solid tumors, and it significantly impedes cancer treatment. Here, we report light-activated hypoxia-responsive nanoparticles NPs-TPZ consisting of 5,10,5,20-tetrakis-(4-aminophenyl)-porphine (TAPP) modified with four azobenzene groups, cyclodextrin (CD), and 3-aminobenzotriazine-1,4-di-N-oxide tirapazamine (TPZ) by the synergy of π-π stacking, host-guest, and hydrophobic interactions for synergistic photodynamic chemotherapy (PDT-CT). Under near-infrared (NIR) irradiation, the process of PDT depletes oxygen and generates singlet oxygen (¹O₂). The induced hypoxia exacerbation further accelerates the release and activation of TPZ. As a result, this hypoxia-responsive nanoparticle provides an effective strategy for the ablation of hypoxic solid tumors by synergistic PDT-CT.