School of Chemistry and Chemical Engineering, State Key Laboratory of Metal Matrix Composites, Frontiers Science Center for Transformative Molecules, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200 240, China.
Shanghai Jiao Tong University Affiliated Sixth People's Hospital South Campus, Shanghai University of Medicine & Health Sciences Affiliated Sixth People's Hospital South Campus, Southern Medical University Affiliated Fengxian Hospital, 6600th Nanfeng Road, Fengxian District, Shanghai, 201 499, China.
Adv Mater. 2021 Mar;33(9):e2006116. doi: 10.1002/adma.202006116. Epub 2021 Jan 27.
Immunotherapy is recognized as one of the most promising approaches to treat cancers. However, its effect in glioblastoma (GBM) treatment is insufficient, which can in part be attributed to the immunosuppressive tumor microenvironment (TME). Microglia and macrophages are the main immune infiltrating cells in the TME of GBM. Unfortunately, instead of initiating the anti-tumor response, GBM-infiltrating microglia and macrophages switch to a tumor-promoting phenotype (M2), and support tumor growth, angiogenesis, and immunosuppression by the release of cytokines. In this work, a virus-mimicking membrane-coated nucleic acid nanogel Vir-Gel embedded with therapeutic miRNA is developed, which can reprogram microglia and macrophages from a pro-invasive M2 phenotype to an anti-tumor M1 phenotype. By mimicking the virus infection process, Vir-Gel significantly enhances the targetability and cell uptake efficiency of the miR155-bearing nucleic acid nanogel. In vivo evaluations demonstrate that Vir-Gel apparently prolongs the circulation lifetime of miR155 and endows it with an active tumor-targeting capability and excellent tumor inhibition efficacy. Owing to its noninvasive feature and effective delivery capability, the virus-mimicking nucleic acid nanogel provides a general and convenient platform that can successfully treat a wide range of diseases.
免疫疗法被认为是治疗癌症最有前途的方法之一。然而，其在胶质母细胞瘤（GBM）治疗中的效果并不理想，这在一定程度上可以归因于免疫抑制性肿瘤微环境（TME）。小胶质细胞和巨噬细胞是 GBM 肿瘤微环境中主要的免疫浸润细胞。不幸的是，浸润 GBM 的小胶质细胞和巨噬细胞并没有引发抗肿瘤反应，而是转变为促进肿瘤生长的表型（M2），通过释放细胞因子来支持肿瘤生长、血管生成和免疫抑制。在这项工作中，开发了一种模拟病毒的膜包覆核酸纳米凝胶 Vir-Gel，其中嵌入了治疗性 miRNA，可将小胶质细胞和巨噬细胞从促侵袭的 M2 表型重编程为抗肿瘤的 M1 表型。通过模拟病毒感染过程，Vir-Gel 显著提高了携带 miR155 的核酸纳米凝胶的靶向性和细胞摄取效率。体内评价表明，Vir-Gel 明显延长了 miR155 的循环半衰期，并赋予其主动的肿瘤靶向能力和优异的肿瘤抑制效果。由于其非侵入性特征和有效的递送能力，这种模拟病毒的核酸纳米凝胶为治疗广泛的疾病提供了一个通用且便捷的平台。
