Near-infrared and tumor environment Co-activated nanoplatform for precise tumor therapy in multiple models

Chemotherapy based on anti-tumor drugs is one of the most commonly utilized approaches for tumor treatment. However, the uncontrollable toxicity of these drugs to healthy tissue, insufficient therapeutic efficiency and chemotherapeutic resistance induced by hypoxic environment in most types of solid tumors still limited the clinical application of chemotherapy. Herein, a smart nanoplatform responsive to near-infrared (NIR) light and tumor-specific microenvironment is developed for precise and effective tumor therapy via chain procedures of rapid hypoxia inhibition, promoted catalytic medicine and low-resistance chemotherapy. The concept is demonstrated by co-encapsulating ferroferric oxide nanoparticles (Fe₃O₄ NPs, photothermal agent and catalyst), calcium peroxide (CaO₂, H₂O₂/O₂ generator) and paclitaxel (PTX, anticancer drug) into an enzyme and thermal breakable capsule, which contained a bilayer shell of hyaluronic acid (HA) and lauric acid (LA). The HA layer serves as tumor target agent to guide the nanoplatform to accumulate in tumor tissue, which would be subsequently degraded by the over-expressed hyaluronidase to expose LA layer for further activation by NIR irradiation. Due to the well-defined melting point of LA at 44°C and excellent photothermal property of Fe₃O₄, the LA layer undertakes a NIR-triggered phase-change to release the encapsulated therapeutic agents (CaO₂, Fe₃O₄ and PTX) for controllable tumor therapy. The exposed CaO₂ would react with water or acid in tumor cells to produce O₂ and H₂O₂, where the O₂ not only press PTX out of the capsule to accelerate its release, but reverse the hypoxic environment to inhibit the hypoxia-induced drug resistance for enhanced chemotherapy. The H₂O₂ would be further converted to cytotoxic hydroxyl radical by Fe₃O₄ via catalytic medicine (Fenton reaction), resulting in an enhanced anticancer activity.