NIR-II 荧光和 PA 成像引导光热治疗中 STING 通路的激活，通过治疗诊断热敏脂质体增强癌症免疫治疗,Journal of Materials Chemistry B

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NIR-II 荧光和 PA 成像引导光热治疗中 STING 通路的激活，通过治疗诊断热敏脂质体增强癌症免疫治疗
Journal of Materials Chemistry B ( IF 6.1 ) Pub Date : 2023-08-09 , DOI: 10.1039/d3tb00711a
Qi Long ₁ , Yuliang Yang ₂ , Fangling Liao ₁ , Haoting Chen ₁ , Dongyue He ₁ , Shengliang Li ₂ , Pengcheng Li ₃ , Weisheng Guo ₁ , Yafang Xiao ₁

Affiliation

光热免疫疗法在有效的癌症治疗方面显示出巨大的潜力。然而，免疫抑制性肿瘤微环境通过抑制树突状细胞 (DC) 成熟和细胞毒性 T 细胞反应，为光热诱导的抗肿瘤免疫形成了沉重的屏障。此外，缺乏可靠的时空成像方式使得光热免疫疗法难以指导肿瘤消融和实时监测治疗结果。在此，我们设计了一种治疗诊断热敏脂质体（PLDD）作为多功能纳米平台，以增强光热免疫疗法的适应性抗肿瘤免疫力，并以实时方式实现多种生物成像模式。PLDD包含两个主要功能成分：多功能光热剂（DTTB）和免疫增强剂STING通路激动剂（DMXAA）。照射后，DTTB产生的热量诱导肿瘤的免疫原性细胞死亡（ICD），并解离热敏脂质体的结构，释放DMXAA，最终激活STING通路，通过增加DC细胞的成熟和促进ICD诱导的免疫反应。 T 细胞募集。此外，PLDD中的DTTB表现出优异的第二近红外（NIR-II）荧光和光声（PA）双模态成像，可以提供肿瘤的全方位信息并指导后续的治疗操作。因此，这种具有光触发促进抗肿瘤免疫和多种时空成像特征的多功能PLDD对于癌症免疫治疗的未来发展具有巨大的潜力。

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NIR-II fluorescence and PA imaging guided activation of STING pathway in photothermal therapy for boosting cancer immunotherapy by theranostic thermosensitive liposomes

Photothermal immunotherapy has shown great potential for efficient cancer treatment. However, the immunosuppressive tumor microenvironment forms a heavy barrier for photothermal-induced anti-tumor immunity by inhibiting dendritic cell (DC) maturation and cytotoxic T cell response. Moreover, the lack of reliable spatiotemporal imaging modalities makes photothermal immunotherapy difficult to guide tumor ablation and monitor therapeutic outcomes in real time. Herein, we designed a theranostic thermosensitive liposome (PLDD) as a versatile nanoplatform to boost the adaptive anti-tumor immunity of photothermal immunotherapy and to achieve multiple bioimaging modalities in a real-time manner. PLDD contains two major functional components: a multifunctional photothermal agent (DTTB) and an immune potentiator STING pathway agonist (DMXAA). Upon irradiation, the heat generated by DTTB induced the immunogenic cell death (ICD) of the tumor and dissociated the structure of thermosensitive liposome to release DMXAA, which ultimately activated the STING pathway and promoted the ICD-induced immune response by increasing DC cell maturation and T cell recruitment. Moreover, the DTTB in PLDD displayed excellent second near-infrared (NIR-II) fluorescence and photoacoustic (PA) dual-modal imaging, which provided omnibearing information on the tumor and guided the subsequent therapeutic operation. Therefore, this versatile PLDD with light-triggered promotion of anti-tumor immunity and multiple spatiotemporal imaging profiles holds great potential for the future development of cancer immunotherapy.

更新日期：2023-08-09

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