Inhibiting Metastasis and Preventing Tumor Relapse by Triggering Host Immunity with Tumor-Targeted Photodynamic Therapy Using Photosensitizer-Loaded Functional Nanographenes.
Inhibiting Metastasis and Preventing Tumor Relapse by Triggering Host Immunity with Tumor-Targeted Photodynamic Therapy Using Photosensitizer-Loaded Functional Nanographenes.
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DOI：
10.1021/acsnano.7b04736
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发表时间：
2017-09
期刊：
影响因子：
17.1
通讯作者：
Xinhe Yu;Duo Gao;Liquan Gao;Jianhao Lai;Chenran Zhang;Yang Zhao;Lijun Zhong;Bing Jia;Fan Wang-Fan
中科院分区：
文献类型：
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作者：
Xinhe Yu;Duo Gao;Liquan Gao;Jianhao Lai;Chenran Zhang;Yang Zhao;Lijun Zhong;Bing Jia;Fan Wang-Fan
有效的癌症治疗不仅取决于破坏原发肿瘤，还取决于调节宿主免疫系统以识别和消除残留的肿瘤细胞并防止转移。在这项研究中，肿瘤整合素αvβ6靶向肽（HK肽）功能化的氧化石墨烯（GO）被光敏剂（HPPH）包被。研究所得的 GO 缀合物 GO(HPPH)-PEG-HK 是否可以破坏原发性肿瘤并增强宿主抗肿瘤免疫力。我们发现 GO(HPPH)-PEG-HK 的肿瘤摄取显着高于 GO(HPPH)-PEG 和 HPPH。使用 GO(HPPH)-PEG 的光动力疗法 (PDT) 可抑制皮下和肺转移小鼠模型中的肿瘤生长。体内光学和单光子发射计算机断层扫描 (SPECT)/CT 成像证明，GO(HPPH)-PEG-HK PDT 引起的肿瘤细胞坏死可激活树突状细胞，并通过增加肿瘤内细胞毒性 CD8+ T 淋巴细胞的浸润来显着阻止肿瘤生长和肺转移。这些结果表明，使用GO(HPPH)-PEG-HK进行肿瘤靶向PDT可以有效消融原发肿瘤并破坏残留肿瘤细胞，从而通过激活宿主抗肿瘤免疫来预防远处转移，并通过刺激免疫记忆来抑制肿瘤复发。
Effective cancer therapy depends not only on destroying the primary tumor but also on conditioning the host immune system to recognize and eliminate residual tumor cells and prevent metastasis. In this study, a tumor integrin αvβ6-targeting peptide (the HK peptide)-functionalized graphene oxide (GO) was coated with a photosensitizer (HPPH). The resulting GO conjugate, GO(HPPH)-PEG-HK, was investigated whether it could destroy primary tumors and boost host antitumor immunity. We found that GO(HPPH)-PEG-HK exhibited significantly higher tumor uptake than GO(HPPH)-PEG and HPPH. Photodynamic therapy (PDT) using GO(HPPH)-PEG suppressed tumor growth in both subcutaneous and lung metastatic mouse models. Necrotic tumor cells caused by GO(HPPH)-PEG-HK PDT activated dendritic cells and significantly prevented tumor growth and lung metastasis by increasing the infiltration of cytotoxic CD8+ T lymphocytes within tumors as evidenced by in vivo optical and single-photon emission computed tomography (SPECT)/CT imaging. These results demonstrate that tumor-targeted PDT using GO(HPPH)-PEG-HK could effectively ablate primary tumors and destroy residual tumor cells, thereby preventing distant metastasis by activating host antitumor immunity and suppressing tumor relapse by stimulation of immunological memory.