Core-shell nanoscale coordination polymers combine chemotherapy and photodynamic therapy to potentiate checkpoint blockade cancer immunotherapy.
Core-shell nanoscale coordination polymers combine chemotherapy and photodynamic therapy to potentiate checkpoint blockade cancer immunotherapy.
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DOI：
10.1038/ncomms12499
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发表时间：
2016-08-17
影响因子：
16.6
通讯作者：
Lin W
中科院分区：
文献类型：
--
作者：
He C;Duan X;Guo N;Chan C;Poon C;Weichselbaum RR;Lin W
晚期结直肠癌是最致命的癌症之一，转移性疾病患者的 5 年生存率仅为 12%。检查点抑制剂，例如抑制 PD-1/PD-L1 轴的抗体，是晚期结肠癌患者最有希望的免疫疗法之一，但其持久缓解率仍然较低。我们在此报告使用免疫原性纳米颗粒来增强 PD-L1 抗体介导的癌症免疫疗法的抗肿瘤功效。纳米配位聚合物（NCP）核壳纳米粒子在核心中携带奥沙利铂，在外壳中携带光敏剂焦脱镁叶绿酸-脂质缀合物（pyrolipid）（NCP@pyrolipid），用于有效的化疗和光动力疗法（PDT）。奥沙利铂和吡啶脂质诱导的 PDT 之间的协同作用可杀死肿瘤细胞并激发免疫反应，导致细胞表面钙网蛋白暴露、抗肿瘤疫苗接种和远隔效应。当与抗 PD-L1 疗法相结合时，NCP@pyrolipid 通过诱导强烈的肿瘤特异性免疫反应来介导光照射的原发肿瘤和未照射的远处肿瘤的消退。 PD-L1 阻断通常对结肠癌患者不太有效。在这里，作者展示了 PD-L1 阻断与携带奥沙利铂和光敏剂的配位聚合物纳米颗粒相结合，在结肠癌转移模型中诱导抗肿瘤免疫的功效。
Advanced colorectal cancer is one of the deadliest cancers, with a 5-year survival rate of only 12% for patients with the metastatic disease. Checkpoint inhibitors, such as the antibodies inhibiting the PD-1/PD-L1 axis, are among the most promising immunotherapies for patients with advanced colon cancer, but their durable response rate remains low. We herein report the use of immunogenic nanoparticles to augment the antitumour efficacy of PD-L1 antibody-mediated cancer immunotherapy. Nanoscale coordination polymer (NCP) core-shell nanoparticles carry oxaliplatin in the core and the photosensitizer pyropheophorbide-lipid conjugate (pyrolipid) in the shell (NCP@pyrolipid) for effective chemotherapy and photodynamic therapy (PDT). Synergy between oxaliplatin and pyrolipid-induced PDT kills tumour cells and provokes an immune response, resulting in calreticulin exposure on the cell surface, antitumour vaccination and an abscopal effect. When combined with anti-PD-L1 therapy, NCP@pyrolipid mediates regression of both light-irradiated primary tumours and non-irradiated distant tumours by inducing a strong tumour-specific immune response. Blockade of PD-L1 is usually not very effective in colon cancer patients. Here, the authors show the efficacy of PD-L1 blockade in combination with coordination polymer nanoparticles carrying oxaliplatin and a photosensitizer to induce anti-tumor immunity in metastatic models of colon cancer.