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0This research article details the development of Ce6@D4-EV, an innovative nanoplatform that utilizes extracellular vesicles to deliver targeted photoimmunotherapy to dense solid tumors. By targeting the protein Midkine (MDK), these engineered vesicles accumulate specifically within the tumor microenvironment, where light activation triggers the destruction of cancer cells and the reprogramming of cancer-associated fibroblasts. This process successfully reduces the extracellular matrix barriers, improves blood flow, and alleviates hypoxia, transforming a resistant environment into one more susceptible to treatment. Furthermore, the therapy induces immunogenic cell death, which activates the cGAS-STING pathway in macrophages to stimulate a robust innate immune response. Preclinical tests demonstrate that this dual stromal-immune remodeling significantly enhances the performance of chemotherapy and immune checkpoint inhibitors. Ultimately, this technology offers a promising strategy for surmounting the physical and immunological defenses of highly desmoplastic malignancies like pancreatic cancer.
References:
Qu C, Liu J, Cen J, et al. Targeted extracellular vesicle-photoimmunotherapy remodels stromal-immune microenvironment to boost chemo-immunotherapy in preclinical models[J]. Cell Reports Medicine, 2026.
