Tumor Microenvironment Stimuli-Responsive Single-NIR-Laser Activated Synergistic Phototherapy for Hypoxic Cancer by Perylene Functionalized Dual-Targeted Upconversion Nanoparticles

Abstract

Although synergistic therapy has shown great promise for effective treatment of cancer, the unsatisfactory therapeutic efficacy of photothermal therapy/photodynamic therapy is resulted from the absorption wavelength mismatch, tumor hypoxia, photosensitizer leakage, and inability in intelligent on-demand activation. Herein, based on the characteristics of tumor microenvironment (TME), such as the slight acidity, hypoxia, and overexpression of H2O2, a TME stimuli-responsive and dual-targeted composite nanoplatform (UCTTD-PC4) is strategically explored by coating a tannic acid (TA)/Fe3+ nanofilm with good biocompatibility onto the upconversion nanoparticles in an ultrafast, green and simple way. The pH-responsive feature of UCTTD-PC4 remains stable during the blood circulation, while rapidly releases Fe3+ in the slightly acidic tumor cells, which results in catalyzing H2O2 to produce O2 and overcoming the tumor hypoxia. Notably, the emission spectrum of the UCTTD perfectly matches the absorption spectrum of the photosensitizer (perylene probe (PC4)) to achieve the enhanced therapeutic effect triggered by a single laser. This study provides a new strategy for the rational design and development of the safe and efficient single near-infrared laser-triggered synergistic treatment platform for hypoxic cancer under the guidance of multimodal imaging.