Engineering Goat Milk-Derived Extracellular Vesicles for Dual-Model Imaging and Anti-Inflammatory Photothermal Therapy of Pancreatic Cancer

As an emerging modality for treatment, photothermal therapy demonstrates significant potential for clinical application. However, the inflammatory reaction after photothermal therapy can lead to tumor recurrence and metastasis. As a novel photothermal agent, biliverdin (BV) also demonstrates a remarkable anti-inflammatory effect. In this study, goat milk-derived extracellular vesicles (GEVs) is used to encapsulate BV. The objective was to enhance tumor uptake of the photothermal agent while alleviating the inflammatory responses associated with photothermal therapy, thereby achieving superior therapeutic outcomes. N3-GEV@BV was successfully synthesized. Additionally, it exhibited notable efficacy in photothermal therapy and demonstrated anti-inflammatory effects in vitro. Utilizing a pretargeting strategy, N3-GEV@BV can accomplish PET/CT imaging in both subcutaneous and orthotopic tumor models. After photothermal treatment, the tumor volume in the N3-GEV@BV+laser group exhibited a significant decrease relative to the other groups, with reductions of up to 1/13 observed. Furthermore, compared to N3-GEV@ICG, mice injected with N3-GEV@BV exhibited lower expression levels of inflammatory factors in both the serum and tumor tissues. As an integrated nanoprobe for diagnosis and treatment, N3-GEV@BV can successfully mediate the photothermal therapy of tumor tissue. Notably, it contributes to enhanced tumor prognosis by mitigating the inflammatory response induced by photothermal therapy, underscoring its broad potential for application.