基于铜（II）金属有机框架（MOFs）的复合纳米探针已被开发出，该探针能够通过光触发调节肿瘤微环境（TME）。该探针将blebbistatin（Bb）封装于MOFs中，并通过表面修饰成纤维母细胞激活蛋白-α靶向肽（Tp）。Tp使纳米探针能够主动靶向癌相关成纤维细胞（CAF），而近红外光则触发MOFs中Cu2+转化为Cu+，导致MOFs崩解并释放出Bb和Cu+。Bb介导光产生的羟基自由基（•OH），从而通过诱导CAF凋亡抑制细胞外基质的产生，有利于纳米探针渗透至深部肿瘤组织。基于Bb和Cu+产生的•OH双通道发生反应，通过不同的机制协同增强TME中的氧化应激，能够诱导免疫原性细胞死亡，激活抗肿瘤免疫应答，并逆转免疫抑制的TME。基于上述TME重塑的这种类型纳米探针的协同抗肿瘤光疗效果已在细胞源性肿瘤异种移植模型中得到明确验证。© 2023 Wiley-VCH GmbH.

A composite nanoagent capable of phototriggered tumor microenvironment (TME) regulation is developed based on copper (II) metal-organic frameworks (MOFs) with encapsulation of blebbistatin (Bb) and surface modification of fibroblast activation protein-αtargeted peptide (Tp). Tp enables active targeting of the nanoagents to cancer-associated fibroblast (CAF) while near-infrared light triggers Cu2+ -to-Cu+ photoreduction in MOFs, which brings about the collapse of MOFs and the release of Bb and Cu+ . Bb mediates photogeneration of hydroxyl radicals (•OH) and therefore inhibits extracellular matrix production by inducing CAF apoptosis, which facilitates the penetration of nanoagent to deep tumor tissue. The dual-channel generation of •OH based on Bb and the Cu+ species, via distinct mechanisms, synergistically reinforces oxidative stress in TME capable of inducing immunogenic cell death, which activates the antitumor immune response and therefore reverses the immunosuppressive TME. The synergistic antitumor phototherapy efficacy of such a type of nanoagent based on the abovementioned TME remodeling is unequivocally verified in a cell-derived tumor xenograft model.© 2023 Wiley-VCH GmbH.