MnO2-melittin nanoparticles serve as an effective anti-tumor immunotherapy by enhancing systemic immune response.
MnO2-melittin nanoparticles serve as an effective anti-tumor immunotherapy by enhancing systemic immune response.
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DOI：
10.1016/j.biomaterials.2022.121706
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发表时间：
2022-08
期刊：
影响因子：
14
通讯作者：
Shupei Tang;Lan Zhou;Hai-yang He;Liwei Cui;Zhi-Juan Ren;Yuhang Tai;Zhunyi Xie;Yi Cao;Dongwei Meng;Qiuli Liu;Yuzhang Wu;Jun Jiang;Xinyuan Zhou
中科院分区：
文献类型：
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作者：
Shupei Tang;Lan Zhou;Hai-yang He;Liwei Cui;Zhi-Juan Ren;Yuhang Tai;Zhunyi Xie;Yi Cao;Dongwei Meng;Qiuli Liu;Yuzhang Wu;Jun Jiang;Xinyuan Zhou
肿瘤疫苗被认为是一种有前途的免疫疗法，以消除恶性肿瘤，旨在引起患者自身的肿瘤特异性免疫反应，对肿瘤细胞。然而，由于抗原免疫原性低、佐剂失效等原因，肿瘤疫苗应用较少。在此，我们设计了肿瘤微环境（TME）响应性MnO2-蜂毒肽纳米颗粒（M-M NPs）。M-M NPs在模拟TME中通过Fenton样反应消耗谷胱甘肽并产生·OH，体外特异性地引起肿瘤细胞死亡，体外激活cGAS-STING通路，并在体外和体内促进抗原呈递细胞的成熟，从而引发全身性抗肿瘤免疫应答，包括增加肿瘤特异性T细胞和产生更多的促炎细胞因子和趋化因子，其均强于MnO2 NPs和蜂毒素。采用小鼠皮下肿瘤模型和B16-F10肺转移模型评价M-M纳米颗粒的抗肿瘤作用，结果表明M-M纳米颗粒对小鼠肿瘤生长和肺转移的抑制作用明显优于MnO2纳米颗粒和蜂毒肽。更重要的是，在双侧肿瘤模型中，只有M-M NP促进树突状细胞的MHC-I交叉修饰以引发肿瘤特异性CD8 + T细胞，并且如果表达同源抗原，则显著抑制左侧肿瘤的生长，同时治疗右侧肿瘤。我们的研究结果提出了一种提高肿瘤疫苗效率的策略，在肿瘤免疫治疗中显示出巨大的治疗效果。
Cancer vaccines are viewed as a promising immunotherapy to eradicate malignant tumors and aim to elicit the patients’ own tumor-specific immune response against tumor cells. However, few cancer vaccines have been applied due to the low immunogenicity of antigen and invalidation of adjuvant. Herein, we designed a tumor microenvironment (TME) responsive MnO2-melittin nanoparticles (M-M NPs). The M-M NPs consumed glutathione and produced •OH via Fenton-like reaction in the mimic TME, specifically caused tumor cell death in vitro, activated cGAS-STING pathway in vitro and promoted the maturation of antigen-presenting cells in vitro andin vivoto elicit systemic anti-tumor immune response including the augmentation of tumor-specific T cells and more productions of pro-inflammatory cytokines and chemokines, which all were stronger than MnO2NPs and melittin. The anti-tumor effects of M-M NPs were evaluated in three subcutaneous tumor models and the B16–F10 lung metastasis model and the tumor growth and lung metastasis were more obviously inhibited in the M-M NPs treated mice, compared with MnO2NPs and melittin treatments. More importantly, only M-M NPs promoted the MHC-I cross-dressing by dendritic cells to prime tumor-specific CD8+T cells and remarkably suppressed the growth of left tumors if express cognate antigen while treating on the right in the bilateral tumor model. Our findings proposed a strategy to enhance the cancer vaccine efficiency which showed great therapeutic effect on tumor immunotherapy.