Graphene oxide arms oncolytic measles virus for improved effectiveness of cancer therapy
Graphene oxide arms oncolytic measles virus for improved effectiveness of cancer therapy
复制标题
氧化石墨烯武装溶瘤麻疹病毒以提高癌症治疗的有效性
DOI：
10.1186/s13046-019-1410-x
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发表时间：
2019-09
影响因子：
11.3
通讯作者：
Wei Jiwu
中科院分区：
文献类型：
--
作者：
Xia Mao;Luo Dongjun;Dong Jie;Zheng Meihong;Meng Gang;Wu Junhua;Wei Jiwu
背景具有复制能力的溶瘤病毒（OV）已被证明是一种有效的抗肿瘤武器。患者体内预先存在的中和抗体对OV的溶瘤疗效是一个巨大的挑战。氧化石墨烯片（Graphene oxide sheets，GOS）具有良好的生物相容性，易于修饰，可用于靶向给药。静脉注射后，通过IVIS Lumina XR系统可视化PEI-GOS-PEG-FA在荷瘤小鼠中的分布。然后，用PEI-GOS-PEG-FA包被溶瘤麻疹病毒（MV-Edm）以形成病毒-GOS复合物（GOS/MV-Edm）。结果GOS/MV-Edm具有较强的感染性和较强的溶瘤作用。在荷瘤小鼠中，GOS/MV-Edm显著提高了肿瘤内的病毒复制，并实现了改善的抗肿瘤效果。然后，我们证实GOS/MV-Edm通过叶酸受体而不是MV-Edm的天然同源受体CD 46进入癌细胞。GOS/MV-Edm在缺乏CD 46的鼠细胞中保持感染性。最后，我们发现，GOS/MV-Edm在体外和体内的抗血清的存在下被有效地保护免于中和。在被动抗血清免疫荷瘤小鼠，生存率显着提高与静脉注射GOS/MV-Edm.ConclusionOur研究结果表明，GOS/MV-Edm显示显着升高的病毒复制内的肿瘤质量，导致改善实体瘤小鼠模型的抗肿瘤效果。我们的研究提供了一种新的策略来武装OV，以实现更有效的癌症治疗。这可能成为癌症患者的一种有前途的治疗策略。
BackgroundReplication-competent oncolytic viruses (OVs) have been proven to be a potent anticancer weapon for clinical therapy. The preexisting neutralizing antibody in patients is a big challenge for oncolytic efficacy of OVs. Graphene oxide sheets (GOS) possess excellent biological compatibility and are easy to decorate for targeted delivery.MethodsWe generated PEI-GOS-PEG-FA (Polyethyleneimine-Graphene oxide sheets-Polyethylene glycol-Folic acid). After intravenous injection, the distribution of PEI-GOS-PEG-FA in tumor-bearing mice was visualized by the IVIS Lumina XR system. Then, the oncolytic measles virus (MV-Edm) was coated with PEI-GOS-PEG-FA to form a viral-GOS complex (GOS/MV-Edm). The oncolytic effects of GOS/MV-Edm were investigated both in vitro and in vivo.ResultsGOS/MV-Edm exhibited higher infectivity and enhanced oncolysis. In tumor-bearing mice, GOS/MV-Edm had significantly elevated viral replication within the tumor mass, and achieved an improved antitumor effect. Then, we confirmed that GOS/MV-Edm entered cancer cells via the folate receptor instead of CD46, a natural cognate receptor of MV-Edm. GOS/MV-Edm remained the infectivity in murine cells that lack CD46. Finally, we found that GOS/MV-Edm was effectively protected from neutralization in the presence of antiserum both in vitro and in vivo. In passively antiserum immunized tumor-bearing mice, the survival was remarkably improved with intravenous injection of GOS/MV-Edm.ConclusionOur findings demonstrate that GOS/MV-Edm displays significantly elevated viral replication within the tumor mass, leading to an improved antitumor effect in solid tumor mouse model. Our study provided a novel strategy to arm OVs for more efficient cancer therapy. That may become a promising therapeutic strategy for cancer patients.
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影响因子：
5.3
作者：
通讯作者：
--
影响因子：
14
作者：
Mendez, Natalie;Herrera, Vanessa;Zhang, Lingzhi;Hedjran, Farah;Feuer, Ralph;Blair, Sarah L.;Trogler, William C.;Reid, Tony R.;Kummel, Andrew C.
通讯作者：
Kummel, Andrew C.
影响因子：
6.7
作者：
Roy DG;Bell JC
通讯作者：
Bell JC
DOI：
10.3390/v8100294
发表时间：
2016-10-22
期刊：
Viruses
影响因子：
--
作者：
Aref S;Bailey K;Fielding A
通讯作者：
Fielding A
影响因子：
2.2
作者：
Ferguson MS;Lemoine NR;Wang Y
通讯作者：
Wang Y