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载抗原磁性脂质体的磁靶向递呈用于主动淋巴结靶向和增强抗肿瘤免疫

Magnetic Delivery of Antigen-Loaded Magnetic Liposomes for Active Lymph Node Targeting and Enhanced Anti-Tumor Immunity.

机构信息

Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, Jiangsu, 210009, P. R. China.

Department of Foodborne Disease and Food Safety Risk Surveillance, Guangzhou Center for Disease Control and Prevention, Guangzhou, Guangdong, 510440, P. R. China.

出版信息

Adv Healthc Mater. 2023 Dec;12(32):e2301232. doi: 10.1002/adhm.202301232. Epub 2023 Sep 22.

Abstract

Therapeutic cancer vaccines offer the greatest advantage of enhancing antigen-specific immunity against tumors, particularly for immunogenic tumors, such as melanoma. However, clinical responses remain unsatisfactory, primarily due to inadequate T cell priming and the development of acquired immune tolerance. A major obstacle lies in the inefficient uptake of antigen by peripheral dendritic cells (DCs) and their migration to lymph nodes for antigen presentation. In this context, the magnetic delivery of antigen-loaded magnetic liposomes (Ag-MLs) to actively target lymph node, is proposed. These magnetic responsive liposomes contain soluble mouse melanoma lysate and iron oxide nanoparticles in the core, along with the immunostimulatory adjuvant CpG-1826 incorporated into the lipid bilayer. When applied through magnetic targeting in the mouse melanoma model, Ag-MLs accumulate significantly in the target lymph nodes. This accumulation results in increased population of active DCs in lymph nodes and cytotoxic T lymphocytes (CTLs) within tumors, correlating with effective tumor growth inhibition. Overall, this study demonstrates the potential of magnetic targeting as an effective strategy for delivering cancer vaccines and activating the immune response, offering a novel platform for cancer immunotherapies.

摘要

治疗性癌症疫苗提供了增强针对肿瘤的抗原特异性免疫的最大优势,特别是对于免疫原性肿瘤,如黑色素瘤。然而,临床反应仍然不尽如人意,主要是由于 T 细胞的初始激活不足和获得性免疫耐受的发展。一个主要的障碍在于外周树突状细胞(DCs)摄取抗原的效率低下,以及它们向淋巴结迁移进行抗原呈递。在这种情况下,提出了将负载抗原的磁性脂质体(Ag-MLs)通过磁性递送来主动靶向淋巴结。这些磁性响应脂质体包含在核心中的可溶性小鼠黑色素瘤裂解物和氧化铁纳米粒子,以及掺入脂质双层中的免疫刺激性佐剂 CpG-1826。当通过在小鼠黑色素瘤模型中的磁性靶向应用时,Ag-MLs 会在靶淋巴结中大量积聚。这种积聚导致淋巴结中活性 DCs 和肿瘤内细胞毒性 T 淋巴细胞(CTL)的数量增加,与有效的肿瘤生长抑制相关。总体而言,这项研究表明磁性靶向作为一种有效的癌症疫苗递送和激活免疫反应的策略具有潜力,为癌症免疫疗法提供了一个新的平台。

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