Ministry of Education Key Laboratory for the Green Preparation and Application of Functional Materials, Hubei Key Laboratory of Polymer Materials, Hubei Collaborative Innovation Center for Advanced Organic Chemical Materials, School of Materials Science and Engineering, Hubei University, Wuhan 430062, China.
Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430034, China.
J Mater Chem B. 2024 Apr 17;12(15):3741-3750. doi: 10.1039/d3tb03016d.
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 -hydroxymethyl acrylamide--(-3-aminopropyl methacrylamide)--DMC block copolymer (NMA--APMA--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.
溶瘤病毒消融肿瘤细胞具有高肿瘤选择性、强免疫原性和低副作用等优点。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且高度可修饰的溶瘤病毒载体，可以提高溶瘤病毒的长期循环稳定性，但肿瘤细胞对其摄取效率有限。在此，我们构建了一种 - 羟甲基丙烯酰胺-(-3- 氨丙基甲基丙烯酰胺)-DMC 嵌段共聚物（NMA-APMA-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稳定性，而且对负载溶瘤病毒也表现出优异的稳定性。数据表明，在培养基中，带正电荷的 NAD/Ad 复合物无论是否存在中和抗体，其转染效果均无明显差异，这意味着 NAD/Ad 介导的阳离子载体具有良好的血清稳定性。只需 10 微克的 NAD 载体即可负载溶瘤病毒，可将转染效率提高 50 倍。细胞实验和小鼠动物实验表明，NAD 载体可显著增强溶瘤病毒的抗肿瘤作用。我们希望这项工作将促进丙烯酰胺作为溶瘤病毒载体的应用，并为丙烯酰胺用于生物医学应用的修饰方法提供新的思路。
