Engineering a Hydrogen-Sulfide-Based Nanomodulator to Normalize Hyperactive Photothermal Immunogenicity for Combination Cancer Therapy
Engineering a Hydrogen-Sulfide-Based Nanomodulator to Normalize Hyperactive Photothermal Immunogenicity for Combination Cancer Therapy
复制标题
DOI：
10.1002/adma.202008481
复制
发表时间：
2021-04-25
影响因子：
29.4
通讯作者：
Dai, Yunlu
中科院分区：
文献类型：
--
作者：
Li, Jie;Xie, Lisi;Dai, Yunlu
光热疗法（PTT）是已知的最有效的癌症治疗策略之一，其突出表现为过度的炎症反应，而消融癌症时具有免疫原性死亡。这种过度活跃的免疫反应可能会超越PTT触发的免疫原性，加剧皮肤灼伤，并导致永久性组织损伤和高姿态肿瘤再生。因此，迫切需要一种先进的光热治疗策略，在病理性和保护性免疫反应之间实现抗癌平衡。在本文中，提出了通过将两亲性缀合的聚合物与基于多硫化物的硫化氢（H2S）供体（2，2 '-联吡啶基四硫化物@CP-PEG）（其中CP =缀合的聚合物并且PEG =聚（乙二醇））整合来调节光热免疫原性的策略。CP具有NIR-II荧光能力和良好的光热效应，可追踪肿瘤进行精确治疗。多硫化物供体可以通过细胞内谷胱甘肽触发释放H2S，从而引起线粒体功能障碍和强大的抗炎作用。最终，这种气体调节的PTT策略显著抑制肿瘤生长并限制PTT诱导的促炎性肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和白细胞介素-1 β（IL-1 β）细胞因子的大小。此外，调节的炎症加速PTT诱导的伤口愈合。因此，具有适应性免疫应答的H2S调节的PTT被推荐作为癌症治疗的高级策略。
Photothermal therapy (PTT), one of the most-potent cancer therapeutic strategies known, is highlighted with excessive inflammatory response, while ablating cancer with immunogenic death. This hyperactive immune response may override PTT-triggered immunogenicity, exacerbate skin empyrosis, and incur permanent tissue injury and high-profile tumor regeneration. Therefore, an anticancer balance between pathological and protective immune response is urgently needed for an advanced photothermal therapeutic tactic. Herein, a gas-modulated photothermal immunogenicity strategy is proposed by integrating an amphiphilic-conjugated polymer with a polysulfide-based hydrogen sulfide (H2S) donor (2,2 '-dipyridyl tetrasulfide@CP-PEG) (where CP = conjugated polymer and PEG = poly(ethylene glycol)). The CP is endowed with NIR-II fluorescence capacity and favorable photothermal effect, tracing the tumor for precise therapeutics. The polysulfide donor can release H2S triggered by intracellular glutathione, which elicits mitochondrial dysfunction and robust anti-inflammation effect. Ultimately, this gas-modulated PTT strategy inhibits tumor growth remarkably and limits the magnitude of PTT-induced proinflammatory tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and interleukin-1beta (IL-1 beta) cytokines. Moreover, the regulated inflammation accelerates PTT-induced wound healing. A H2S-modulated PTT with adaptive immune response is thus recommended as an advanced strategy to cancer therapeutics.