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Spatial and Temporal Control of T Cell Activation Using a Photoactivatable Agonist
Published on: April 25, 2018
Spatiotemporal-Controlled Nanoagonists Triggered STING Activation for Cascade-Amplified Photothermal
1Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, Department of Radiation Oncology and Department of Head and Neck Oncology, West China Hospital, Sichuan University, Chengdu 610041, China.
None:
Triple-negative breast cancer is an aggressive subtype of breast cancer characterized by rapid disease progression and a high risk of metastasis. The advent of immunotherapy has revolutionized the treatment paradigm for breast cancer. Herein, a manganese-based nanoagonist (FA-IR780/EGCG@MnO2) featuring mitochondrial targeting and photothermal therapy (PTT) was constructed for STING activation and photothermal metalloimmunotherapy. The engineered FA-IR780/EGCG@MnO2 was constructed to enable the generation of mitochondria-targeted reactive oxygen species under laser irradiation to release mitochondrial DNA (mtDNA) and induce immunogenic cell death. The released mtDNA, as an endogenous danger-associated molecular pattern, could activate the STING pathway. Concurrently, Mn2+ further enhanced the activation of the STING pathway. By combining the synergistically enhanced the activation of the STING pathway, the engineered nanoagonist facilitated the DC maturation and T lymphocyte infiltration, resulting in long-term immune memory to inhibit tumor growth. This study revealed the potential combination of metalloimmunotherapy and PTT for rational regulation of the immune microenvironment.
