磁性递送载有抗原的磁性脂质体用于活性淋巴结靶向输送与增强抗肿瘤免疫。
Magnetic Delivery of Antigen-Loaded Magnetic Liposomes for Active Lymph Node Targeting And Enhanced Anti-Tumor Immunity.
发表日期:2023 Sep 14
作者:
Jingyi Sheng, Yang Liu, He Ding, Linyuan Wu, Lan Liu, Guangxiang Si, Yan Shen, Fang Yang, Ning Gu
来源:
Cellular & Molecular Immunology
摘要:
治疗性癌症疫苗在增强抗原特异性免疫应对肿瘤方面具有最大优势,尤其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细胞初次免疫不足和获得性免疫耐受的发展。主要障碍在于外周树突状细胞(DCs)对抗原的摄取效率低和其迁移到淋巴结进行抗原呈递。在这种情况下,我们提出通过磁性送达抗原装载的磁性脂质体(Ag-MLs)以主动靶向淋巴结。这些磁响应性脂质体的核心含有可溶性小鼠黑色素瘤裂解物和铁氧化物纳米颗粒,脂质双层中还包含免疫刺激佐剂CpG-1826。在小鼠黑色素瘤模型中通过磁性靶向应用,Ag-MLs在目标淋巴结中显著积累。这种积累导致淋巴结中活跃DCs的人口增加以及肿瘤内细胞毒性T淋巴细胞(CTLs)的增加,与有效抑制肿瘤生长相关。总体而言,我们的研究展示了磁性靶向作为有效的癌症疫苗传递和激活免疫应策略的潜力,为癌症免疫疗法提供了一种新平台。本文受版权保护。版权所有。
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, we propose the magnetic delivery of antigen-loaded magnetic liposomes (Ag-MLs) to actively target lymph node. 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, our 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. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.