IR780-Loaded E. coli Membrane Nanovesicles Combined with Photodynamic Therapy to Enhance Immunogenicity in Osteosarcoma

The immunosuppressive microenvironment of osteosarcoma (OS) and the inherent toxicity of current neoadjuvant chemotherapy present significant challenges in treatment, highlighting the urgent need for innovative therapeutic approaches. Photodynamic therapy (PDT) is a promising noninvasive alternative; however, its clinical application is limited by the poor stability of traditional photosensitizers (PS), insufficient reactive oxygen species (ROS) production, and a weak antitumor immune response. Given these limitations, a combination therapy that enhances PDT’s therapeutic efficacy while stimulating immune activation could offer a more effective strategy. In this study, we developed a biomimetic nanomedicine (IR780@EM) by integrating the near-infrared photosensitizer IR780 with Escherichia coli-derived membrane nanovesicles (EM). This approach synergistically combines localized PDT with systemic antitumor immunity, leading to enhanced ROS generation and promoting M2-to-M1 polarization of macrophages in tumor, thereby activating the immune system and driving OS regression. Unlike conventional chemotherapy-based treatments, this strategy not only addresses the key limitations of PDT─insufficient ROS production and limited immune activation─but also helps overcome chemotherapy resistance and convert immunologically “cold” tumors into “hot” tumors, thereby improving therapeutic outcomes. This EM-based nanotherapeutic strategy holds significant translational potential for optimizing PDT efficacy and offers a multidimensional treatment approach for OS.