MRI-guided photothermal/photodynamic immune activation combined with PD-1 inhibitor for the multimodal combination therapy of melanoma and metastases

Abstract

Non-invasive image-guided precise photothermal/photodynamic therapy (PTT/PDT) has been proven an effective local treatment modality, but incompetent against metastases. Hence the combination of local PTT/PDT and systemic immunotherapy would be a promising strategy for tumor eradication. Herein, a MRI-visualized PTT/PDT agent (SIDP NMs) was constructed, and the efficacy of its multimodal combination with PD-1 inhibitor in the treatment of melanoma and metastases was studied. Due to the hydrophobic encapsulation of indocyanine green (ICG) within the micellar core, SIDP NMs exhibited excellent photothermal/photodynamic properties and stability under 808 nm near-infrared laser (NIR). In vitro cell experiments showed that SIDP NMs had a good killing effect. After incubating with B16-F10 cells for 24 h and irradiating with 808 nm laser for 10 min, cell viability decreased significantly. Magnetic resonance imaging experiments in melanoma-bearing mice have shown that the dynamic distribution of SIDP NMs in tumor tissue could be monitored by T2WI and T2-MAP noninvasively due to the presence of superparamagnetic iron oxide nanocrystal (SPIO) in SIDP NMs. When the 808 nm laser was irradiated at the maximum focusing time point shown by MRI, the temperature of the tumor area rapidly increased from 32 °C to 60.7 °C in five minutes. In mouse melanoma ablation and distant tumor immunotherapy studies, SIDP NMs provided excellent MRI-guided photothermal/photodynamic therapy results and, when combined with PD-1 inhibitor, have great potential to cure primary tumors and eradicate metastases.