Oxidation-sensitive polymeric nanocarrier-mediated cascade PDT chemotherapy for synergistic cancer therapy and potentiated checkpoint blockade immunotherapy

Abstract

Photodynamic therapy (PDT) is a promising therapeutic strategy for the clinical treatment of laryngeal cancer, and nanocarriers could be easily combined PDT with conventional chemotherapy for enhanced therapeutic outcomes. However, the encapsulation of photosensitizers (PS) and chemotherapy drugs into conventional nanocarriers achieves only a simple combination without synergistic effects. Herein, we explored an oxidation-sensitive polyphosphoester (PPE)-based nanocarrier to co-encapsulate chlorin e6 (Ce6) and docetaxel (Dtxl) for synergistic laryngeal cancer therapy. During the PDT process, the produced ROS not only induced cell apoptosis but also triggered the release of Dtxl through the hydrophobic to hydrophilic transition of the PPE core, resulting in a cascade PDT/chemotherapy to elicit a synergistic anticancer effect for the complete suppression of laryngeal cancer growth. Moreover, this oxidation-sensitive nanocarrier-mediated cascade PDT/chemotherapy can also induce an effective antitumor immune response via the immunogenic cell death effect (ICD) and potentiate the effectiveness of immune checkpoint blockade (ICB) antibodies to inhibit distant tumor growth.