Chlorin-Based Nanoscale Metal-Organic Framework Systemically Rejects Colorectal Cancers via Synergistic Photodynamic Therapy and Checkpoint Blockade Immunotherapy.
Chlorin-Based Nanoscale Metal-Organic Framework Systemically Rejects Colorectal Cancers via Synergistic Photodynamic Therapy and Checkpoint Blockade Immunotherapy.
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DOI：
10.1021/jacs.6b06663
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发表时间：
2016-09-28
影响因子：
15
通讯作者：
Lin W
中科院分区：
文献类型：
--
作者：
Lu K;He C;Guo N;Chan C;Ni K;Weichselbaum RR;Lin W
光动力疗法（PDT）可以破坏局部肿瘤并使正常组织损伤最小化，但在消除转移方面无效。检查点阻断免疫疗法最近在临床上取得了成功，但由于宿主免疫系统的活化不足，大多数癌症的全身性抗肿瘤应答率有限。在这里，我们描述了一种治疗策略，该治疗策略通过新的基于二氢卟酚的纳米级金属有机框架（nMOF），TBC-Hf和抑制吲哚胺2，3-双加氧酶（IDO）的小分子免疫治疗剂结合PDT，封装在nMOF通道中以诱导全身抗肿瘤免疫。协同联合治疗在结直肠癌模型中实现了有效的局部和远处肿瘤排斥。我们检测到在免疫系统活化后肿瘤微环境中增加的T细胞浸润，所述免疫系统与通过小分子免疫治疗剂的IDO抑制和通过PDT诱导的免疫原性细胞死亡的组合。我们还阐明了潜在的免疫学机制，并揭示了在这种联合治疗中中性粒细胞和B细胞在向T细胞呈递肿瘤相关抗原中的代偿作用。我们认为，nMOF激活的PDT有可能显著增强检查点阻断癌症免疫治疗，为许多难治性癌症的治疗提供临床益处。
Photodynamic therapy (PDT) can destroy local tumors and minimize normal tissue damage, but is ineffective at eliminating metastases. Checkpoint blockade immunotherapy has enjoyed recent success in the clinic, but only elicits limited rates of systemic antitumor response for most cancers due to insufficient activation of the host immune system. Here we describe a treatment strategy that combines PDT by a new chlorin-based nanoscale metal–organic framework (nMOF), TBC-Hf, and a small-molecule immunotherapy agent that inhibits indoleamine 2,3-dioxygenase (IDO), encapsulated in the nMOF channels to induce systemic antitumor immunity. The synergistic combination therapy achieved effective local and distant tumor rejection in colorectal cancer models. We detected increased T cell infiltration in the tumor microenvironment after activation of the immune system with the combination of IDO inhibition by the small-molecule immunotherapy agent and immunogenic cell death induced by PDT. We also elucidated the underlying immunological mechanisms and revealed compensatory roles of neutrophils and B cells in presenting tumor-associated antigens to T cells in this combination therapy. We believe that nMOF-enabled PDT has the potential to significantly enhance checkpoint blockade cancer immunotherapy, affording clinical benefits for the treatment of many difficult-to-treat cancers.
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影响因子：
16.6
作者：
Carter, Kevin A.;Shao, Shuai;Hoopes, Matthew I.;Luo, Dandan;Ahsan, Bilal;Grigoryants, Vladimir M.;Song, Wentao;Huang, Haoyuan;Zhang, Guojian;Pandey, Ravindra K.;Geng, Jumin;Pfeifer, Blaine A.;Scholes, Charles P.;Ortega, Joaquin;Karttunen, Mikko;Lovell, Jonathan F.
通讯作者：
Lovell, Jonathan F.
用于聚集诱导发射引导精确光动力治疗的比例生物传感器
影响因子：
17.1
作者：
Han, Kai;Wang, Shi-Bo;Zhang, Xian-Zheng
通讯作者：
Zhang, Xian-Zheng
用于荧光成像引导的光动力疗法的光敏剂共轭二氧化硅涂层金纳米团簇。
影响因子：
14
作者：
Huang, Peng;Lin, Jing;Wang, Shouju;Zhou, Zhijun;Li, Zhiming;Wang, Zhe;Zhang, Chunlei;Yue, Xuyi;Niu, Gang;Yang, Min;Cui, Daxiang;Chen, Xiaoyuan
通讯作者：
Chen, Xiaoyuan
影响因子：
15
作者：
Lu K;He C;Lin W
通讯作者：
Lin W
影响因子：
11.2
作者：
Kousis, Phiaretos C.;Henderson, Barbara W.;Gollnick, Sandra O.
通讯作者：
Gollnick, Sandra O.