Copper-Doped Platinum/Metal-Organic Framework Nanostructures for Imaging-Guided Photothermal and H₂O₂ Self-Supplying Photodynamic/Photothermal/Chemodynamic Therapy

Simultaneous photodynamic/photothermal therapy (PDT/PTT) is a combination cancer treatment that combines the principles of both PDT and PTT to achieve an effective and comprehensive attack on cancer cells. However, both approaches require an external light source to generate reactive oxygen species (ROS) and thermal heat, which could potentially hinder the therapeutic efficacy due to the low tissue penetration of light in vivo. Chemodynamic therapy (CDT) is a type of therapy that uses the ROS generated by the chemical reaction between a prodrug and a catalyst to kill cancer cells. We developed a combination therapy of three modalities (PTT/PDT/CDT) using the metal-organic framework (MOF). The Cu²⁺-doped MOF PCN-224 nanostructures modified with platinum (Pt) cluster and folic acid (FA) provided excellent tumor targeting, photothermal conversion ability, and ROS generated by the Pt cluster and Cu²⁺ under 650 nm light irradiation. Moreover, this multimodel nanocomposite had an extremely low dark toxicity but excellent phototoxicity under the combination laser irradiation at 650 nm, both in vitro and in vivo. Therefore, our prepared folic acid-conjugated PCN-224/Pt/Cu²⁺ (FA-PPC) nanosphere could be applied as a very promising multimodal phototherapeutic agent for enhanced cancer therapy in future clinical applications.