Synergizing Upconversion Nanophotosensitizers with Hyperbaric Oxygen to Remodel Extracellular Matrix for Enhanced Photodynamic Cancer Therapy.

Photodynamic therapy (PDT) holds great promise as a non-invasive and selective cancer therapeutic treatment in preclinic research and clinical practise; however, it has limited efficacy in the ablation of deep-seated tumor due to hypoxia-associated circumstance and poor penetration of photosensitizers to cancer cells away from the blood vessels. To tackle the obstacles, we propose a therapeutic strategy that synergizes upconversion nanophotosensitizers (UNPSs) with hyperbaric oxygen (HBO) to remodel the extracellular matrix for enhanced photodynamic cancer therapy. The UNPSs are designed to have a Nd3+-sensitized sandwiched structure, wherein the upconversion core serves as light transducers to transfer energy to the neighbouring photosensitizers to produce reactive oxygen species (ROS). With HBO, photodynamic process can generate abundant ROS in the intrinsically hypoxic tumor. It is revealed for the first time that HBO-assist PDT decomposes collagen in the extracellular matrix of tumor and thus facilitates the diffusion of oxygen and penetration of UNPSs into the deeper area of tumor. Such a synergic effect eventually results in a significantly enhanced therapeutic efficacy at a low laser power density as compared with that using UNPSs alone. In view of its good biosafety, the HBO-assisted and UNPSs-mediated photodynamic therapy provides new possibilities for treatment of solid tumors.