Visible-Light-Triggered Prodrug Nanoparticles Combine Chemotherapy and Photodynamic Therapy to Potentiate Checkpoint Blockade Cancer Immunotherapy
- Visible-Light-Triggered Prodrug Nanoparticles Combine Chemotherapy and Photodynamic Therapy to Potentiate Checkpoint Blockade Cancer Immunotherapy
- 김광명; 윤홍열; 조한희; 최지웅; 양수아; 김정래; 김진성; 문유정; 윤완수; 심만규; 황희숙
- Issue Date
- ACS Nano
- VOL 15, NO 7-12098
- Immune checkpoint blockade is a promising approach for cancer immunotherapy, but many patients do not respond due to the immunosuppressive tumor microenvironment (ITM). Herein, we propose visible-light-triggered prodrug nanoparticles (LT-NPs) for reversing ITM into high immunogenic tumors to potentiate checkpoint blockade immunotherapy. The photosensitizer (verteporfin; VPF), cathepin B-specific cleavable peptide (FRRG), and doxorubicin (DOX) conjugates are self-assembled into LT-NPs without any additional carrier material. The LT-NPs are specifically cleaved to VPF and DOX in cathepsin B-overexpressing cancer cells, thereby inducing cancer-specific cytotoxicity and immunogenic cell death (ICD) upon visible light irradiation. In tumor models, LT-NPs highly accumulate within tumors via the enhanced permeability and retention effect, and photochemotherapy of VPF and DOX induces effective ICD and maturation of dendritic cells to stimulate cross-presentation of cancer-antigens to T cells. Furthermore, LT-NPs with PD-L1 blockade greatly inhibit tumor growth, tumor recurrence, and lung metastasis by initiating a strong antitumor immune response. The photochemotherapy by LT-NPs provides a promising strategy for effective checkpoint blockade immunotherapy.
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