Immune remodeling triggered by photothermal therapy with semiconducting polymer nanoparticles in combination with chemotherapy to inhibit metastatic cancers

Abstract

Photothermal therapy (PTT) based on semiconducting polymer nanoparticles (SPNs) is a promising strategy to treat solid tumors, but its ability to combine with chemotherapy for immune remodeling to efficiently suppress metastatic cancers has rarely been studied. Here, we demonstrate that PTT combined with chemotherapy can efficiently elicit immunity to suppress metastatic tumor growth. Specifically, we rationally designed a new SPN (PDPSe NPs) as a photothermal agent for PTT with a large mass extinction coefficient in the near-infrared region (e.g., 44.9 L g⁻¹ cm⁻¹ at 808 nm), high photothermal conversion efficiency (62.5%) and excellent biocompatibility. A hypoxia-activated anti-tumor drug, tirapazamine (TPZ), was selected for chemotherapy. Strikingly, the combination therapy not only induced tumor cell death in the primary tumor, but also effectively suppressed the growth of distant tumors (mimicking metastatic tumors) without PTT. Importantly, the combined therapies exhibit synergistic effects on immune remodeling. Immunofluorescence data suggest that the inhibition of metastatic tumor growth is attributed to the immune remodeling triggered by PTT and chemotherapy. This work demonstrates a new paradigm of utilizing PTT together with hypoxia-activated drugs to effectively retard metastatic tumor growth.