Chen Yun, He Peiying, Jana Deblin, Wang Dongdong, Wang Menghao, Yu Peiyuan, Zhu Wei, Zhao Yanli
MOE International Joint Research Laboratory on Synthetic Biology and Medicines, School of Biology and Biological Engineering, South China University of Technology, Guangzhou, 510006, P. R. China.
Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, Singapore, 637371, Singapore.
Adv Mater. 2022 May;34(21):e2201706. doi: 10.1002/adma.202201706. Epub 2022 Apr 24.
Although photothermal immunotherapy (PTI) is a compelling strategy for tumor therapy, the development of promising photothermal agents to overcome the insufficient immunogenicity of tumor cells and the poor immune response encountered in PTI is still challenging. Herein, commercial small-molecule-based organic metal adjuvants (OMAs) are presented, with second near-infrared photoacoustic and photothermal properties as well as the ability to perturb redox homeostasis to potentiate immunogenicity and immune responsiveness. OMAs, assembled from charge-transfer complexes and characterized by a broad substrate scope, high accessibility, and flexibly tuned optical properties, demonstrate strong phototherapeutic and adjuvant abilities via the depletion of glutathione and cysteine, and subsequently elicit systemic immunity by evoking immunogenic cell death, promoting dendritic cell maturation, and increasing T cell infiltration. Furthermore, programmed cell death protein 1 antibody can be employed to synergize with OMAs to suppress tumor immune evasion and ultimately improve the treatment outcomes. This study unlocks new paradigms to provide a versatile OMA-based scaffold for future practical applications.
尽管光热免疫疗法（PTI）是一种极具吸引力的肿瘤治疗策略，但开发有前景的光热剂以克服肿瘤细胞免疫原性不足以及PTI中遇到的免疫反应不佳等问题仍然具有挑战性。在此，我们展示了基于商业小分子的有机金属佐剂（OMAs），它们具有二次近红外光声和光热特性，以及扰乱氧化还原稳态以增强免疫原性和免疫反应性的能力。OMAs由电荷转移复合物组装而成，具有广泛的底物范围、高可及性和可灵活调节的光学性质，通过消耗谷胱甘肽和半胱氨酸展现出强大的光治疗和佐剂能力，随后通过引发免疫原性细胞死亡、促进树突状细胞成熟和增加T细胞浸润来引发全身免疫。此外，程序性细胞死亡蛋白1抗体可与OMAs协同作用，以抑制肿瘤免疫逃逸并最终改善治疗效果。本研究开启了新的范例，为未来的实际应用提供了一种通用的基于OMA的支架。
