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Enhancing oncolytic virus efficiency with methionine and N-(3-aminoprolil)methacrylamide modified acrylamide cationic block polymer
Journal of Materials Chemistry B ( IF 7 ) Pub Date : 2024-03-15 , DOI: 10.1039/d3tb03016d
Gong Chen 1 , Yuan Yuan 2, 3, 4 , Ying Li 2, 3 , Qianyuan He 1 , Zizhen Qin 5 , Han Hu 1 , Congcong Gao 1 , Zushun Xu 1 , Qi Xu 1 , Qinglei Gao 2, 3 , Fei Li 2, 3
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Oncolytic virus ablation of tumor cells has the advantages of high tumor selectivity, strong immunogenicity, and low side effects. However, the recognition and clearance of oncolytic viruses by the immune system are the main factors limiting their anti-tumor efficiency. As a highly biosafe and highly modifiable oncolytic virus vector, acrylamide can improve the long-term circulation of oncolytic viruses. Still, it is limited in its uptake efficiency by tumor cells. Herein, we constructed an N-hydroxymethyl acrylamide-b-(N-3-aminopropyl methacrylamide)-b-DMC block copolymer (NMA-b-APMA-b-DMA, NAD) as an oncolytic virus carrier, which not only improves the long-term circulation of oncolytic viruses in the body but also shows excellent stability for loading an oncolytic virus. The data shows that there was no obvious difference in the transfection effect of the NAD/Ad complex with or without neutralizing antibodies in the medium, which meant that the cationic carrier mediated by NAD/Ad had good serum stability. Only 10 micrograms of NAD carrier are needed to load the oncolytic virus, which can increase the transfection efficiency by 50 times. Cell experiments and mouse animal experiments show that NAD vectors can significantly enhance the anti-tumor effect of oncolytic viruses. We hope that this work will promote the application of acrylamide as an oncolytic virus vector and provide new ideas for methods to modify acrylamide for biomedical applications.

中文翻译:

使用蛋氨酸和 N-(3-aminoprolil)methacrylamide 改性丙烯酰胺阳离子嵌段聚合物提高溶瘤病毒效率

溶瘤病毒消融肿瘤细胞具有肿瘤选择性高、免疫原性强、副作用低等优点。然而,免疫系统对溶瘤病毒的识别和清除是限制其抗肿瘤效率的主要因素。丙烯酰胺作为一种高度生物安全、高度可修饰的溶瘤病毒载体,可以改善溶瘤病毒的长期循环。尽管如此,它被肿瘤细胞的吸收效率仍然有限。在此,我们构建了N-羟甲基丙烯酰胺-b- ( N -3-氨丙基甲基丙烯酰胺)-b - DMC嵌段共聚物(NMA -b -APMA- b -DMA,NAD)作为溶瘤病毒载体,不仅提高了溶瘤病毒在体内的长期循环,而且对于装载溶瘤病毒也表现出优异的稳定性。数据显示,培养基中添加或不添加中和抗体的NAD/Ad复合物的转染效果没有明显差异,这意味着NAD/Ad介导的阳离子载体具有良好的血清稳定性。装载溶瘤病毒仅需10微克NAD载体,可将转染效率提高50倍。细胞实验和小鼠动物实验表明,NAD载体可以显着增强溶瘤病毒的抗肿瘤作用。我们希望这项工作能够促进丙烯酰胺作为溶瘤病毒载体的应用,并为丙烯酰胺的修饰方法用于生物医学应用提供新的思路。
更新日期:2024-03-15
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