NIR-light-intensified hypoxic microenvironment for cascaded supra-prodrug activation and synergistic chemo/photodynamic cancer therapy

• Main Authors: Chen, Hongzhong, Sun, Tao, Zeng, Weiwei, Zeng, Xiaowei, Mei, Lin, Jiang, Chen, Zhao, Yanli
• Other Authors: School of Physical and Mathematical Sciences
• Format: Article
• Language: English
• Published: 2022
• Subjects: Science::Chemistry; Hypoxia; Cancer
• Online Access: https://hdl.handle.net/10356/155937
• Institution: Nanyang Technological University

Despite that photodynamic therapy (PDT) has promising clinical prospect, its therapeutic efficacy is still restricted by the hypoxic tumor microenvironment (TME). Therefore, how to suitably employ the tumor hypoxia is vital for optimizing PDT. Herein, we developed a hypoxia-activated prodrug for combination therapy with PDT. A hypoxia-responsive camptothecin (CPT)-based prodrug and a near-infrared (NIR) BODIPY photosensitizer were co-loaded within a -cyclodextrin-based polymer through supramolecular host-guest recognition to obtain nanoparticles named as CPT-BODIPY-PNs. After being internalized by tumor, the oxygen in the tumor tissues was rapidly consumed by the photosensitizer moiety to generate reactive oxygen species under NIR irradiation. The prodrug was efficiently activated under this intensified hypoxic condition to release chemotherapeutic CPT drug. This system makes the best use of hypoxia TME to achieve effectively combined PDT and chemotherapy, offering an approach for cancer treatment.