NIR‐triggered Tandem Photothermal and Photochemical Cancer Therapy Based on Nanoscale MOFs under Hypoxic Conditions

Abstract Due to the limited penetration depth of visible light and insufficient oxygen supply in hypoxic tumor tissues, the development of near‐infrared (NIR) triggered and oxygen‐independent photodynamic therapy (PDT) to generate active radicals is necessary for cancer treatment. Herein, we developed a NIR‐triggered photothermal therapy (PTT) and oxygen‐independent PDT system based on metal‐organic frameworks (MOFs), which integrated indocyanine green (ICG) and 2,2’‐azobis[2‐(2‐imidazolin‐2‐yl)propane] dihydrochloride (AIPH) as NIR‐triggered photothermal units and temperature‐sensitive free radical initiator into ZIF‐8, respectively. AIPH was introduced into ZIF‐8 via a one‐pot strategy with high loading capacity (125 mg g⁻¹). Through the irradiation of 808 nm laser, the ICG units could efficiently absorb NIR light to rapidly raise the local temperature to 44 °C within 3 minutes. Meanwhile, the local high temperature further induced the AIPH to continuously generate toxic alkyl radicals (R−C⋅). The combination of PTT and free radical therapy is significantly better than the single treatment mode. More importantly, the NIR‐triggered synergistic therapy could induce extensive apoptosis of cancer cells in hypoxic conditions, which sheds new light on the development of MOFs‐based photochemical therapy platform in the actual tumor microenvironment.