Near-Infrared II Phototherapy Induces Deep Tissue Immunogenic Cell Death and Potentiates Cancer Immunotherapy
Near-Infrared II Phototherapy Induces Deep Tissue Immunogenic Cell Death and Potentiates Cancer Immunotherapy
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近红外 II 光疗可诱导深层组织免疫原性细胞死亡并增强癌症免疫治疗
DOI：
10.1021/acsnano.9b06040
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发表时间：
2019-10-01
期刊：
影响因子：
17.1
通讯作者：
Wang, Yucai
中科院分区：
文献类型：
--
作者：
Ma, Yinchu;Zhang, Yuxue;Wang, Yucai
实体瘤的深床和内床缺乏淋巴细胞浸润，并受到各种免疫逃逸机制的影响。逆转肿瘤深处的免疫抑制在临床癌症治疗中至关重要，但它仍然是一个巨大的挑战。在这项工作中，我们已经证明了使用第二窗口近红外（NIR(II)）光热治疗在实体肿瘤中触发更均匀和更深层次的免疫原性癌细胞死亡，从而引发先天性和适应性免疫反应，以控制肿瘤和预防转移。具体而言，通过控制金纳米颗粒在流体脂质体上的自组装，构建了具有相似组件、结构和光热转换效率，但在红光、近红外(I)和近红外（II）生物窗口中的吸收不同的光热换能器。在体外，光热处理诱导免疫原性细胞死亡（ICD），并伴有损伤相关分子模式（DAMPs）的释放，而与入射激光的波长无关。在体内，近红外（II）光导致DAMPs在肿瘤深部更均匀地释放和分布。通过诱导ICD， NIR（II）光热疗法同时触发了先天性和适应性免疫反应，并有效地控制了肿瘤，在癌症疫苗接种试验中，5/8的小鼠保持无肿瘤。此外，NIR（II）光热治疗联合检查点阻断治疗对原发性和远处肿瘤均有长期的肿瘤控制作用。最后，使用系统给药的二维聚吡咯纳米片作为近红外（II）传感器，我们通过协同光热免疫反应实现了对全身肿瘤转移的显著治疗效果。
The deep and inner beds of solid tumors lack lymphocytic infiltration and are subjected to various immune escape mechanisms. Reversing immunosuppression deep within the tumor is vital in clinical cancer therapy, however it remains a huge challenge. In this work, we have demonstrated the use of a second window near-infrared (NIR(II)) photothermal treatment to trigger more homogeneous and deeper immunogenic cancer cell death in solid tumors, thereby eliciting both innate and adaptive immune responses for tumor control and metastasis prevention. Specifically, photothermal transducers with similar components, structures, and photothermal conversion efficiencies, but different absorptions in red light, NIR(I), and NIR(II) biowindows, were constructed by controlling the self-assembly of gold nanoparticles on fluidic liposomes. In vitro, photothermal treatments induced immunogenic cell death (ICD) that were accompanied by the release of damage-associated molecular patterns (DAMPs) regardless of the wavelength of incident lasers. In vivo, NIR(II) light resulted in a more homogeneous release and distribution of DAMPs in the deeper parts of the tumors. With the induction of ICD, NIR(II) photothermal therapy simultaneously triggered both innate and adaptive immune responses and enabled efficient tumor control with 5/8 of the mice remaining tumor-free in the cancer vaccination assay. Additionally, the NIR(II) photothermal treatment in combination with checkpoint blockade therapy exerted long-term tumor control over both primary and distant tumors. Finally, using systemically administered two-dimensional polypyrrole nanosheets as a NIR(II) transducer, we achieved striking therapeutic effects against whole-body tumor metastasis via a synergistic photothermal-immunological response.