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

Abstract: 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.

DOI: 10.1016/j.apmt.2021.101133