Inhibiting Metastasis and Preventing Tumor Relapse by Triggering Host Immunity with Tumor-Targeted Photodynamic Therapy Using Photosensitizer-Loaded Functional Nanographenes,ACS Nano

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Inhibiting Metastasis and Preventing Tumor Relapse by Triggering Host Immunity with Tumor-Targeted Photodynamic Therapy Using Photosensitizer-Loaded Functional Nanographenes
ACS Nano ( IF 15.8 ) Pub Date : 2017-09-18 00:00:00 , DOI: 10.1021/acsnano.7b04736
Xinhe Yu ₁ , Duo Gao ₁ , Liquan Gao ₁ , Jianhao Lai ₁ , Chenran Zhang ₁ , Yang Zhao ₁ , Lijun Zhong ₂ , Bing Jia _{1,

2} , Fan Wang _{1,

3} , Xiaoyuan Chen ₄ , Zhaofei Liu ₁

Affiliation

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.

中文翻译：

通过使用载有光敏剂的功能性纳米石墨烯靶向肿瘤的光动力疗法，通过触发宿主免疫来抑制转移并预防肿瘤复发。

有效的癌症治疗不仅取决于破坏原发性肿瘤，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，肿瘤整联蛋白αvβ6靶向肽（HK肽）功能化的氧化石墨烯（GO）涂有光敏剂（HPPH）。研究了所得GO偶联物GO（HPPH）-PEG-HK是否可以破坏原发肿瘤并增强宿主抗肿瘤免疫力。我们发现GO（HPPH）-PEG-HK比GO（HPPH）-PEG和HPPH表现出明显更高的肿瘤吸收。使用GO（HPPH）-PEG的光动力疗法（PDT）抑制了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成像证明了肿瘤内的⁺ T淋巴细胞。这些结果表明，使用GO（HPPH）-PEG-HK靶向肿瘤的PDT可以有效消融原发性肿瘤并破坏残留的肿瘤细胞，从而通过激活宿主抗肿瘤免疫力并通过刺激免疫记忆抑制肿瘤复发来预防远处转移。

更新日期：2017-09-19

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