Liposomes-coated gold nanocages with antigens and adjuvants targeted delivery to dendritic cells for enhancing antitumor immune response

Liposomes-coated gold nanocages with antigens and adjuvants targeted delivery to dendritic cells for enhancing antitumor immune response
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脂质体包被的金纳米笼将抗原和佐剂靶向递送至树突状细胞以增强抗肿瘤免疫反应

DOI:
10.1016/j.biomaterials.2017.09.029
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发表时间:
2017-12-01
期刊:
影响因子:
14
通讯作者:
Tao, Juan
Tao, Juan
中科院分区:
工程技术1区
文献类型:
--
作者:
Liang, Ruijing;Xie, Jun;Tao, Juan

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对于基于纳米疫苗的癌症免疫治疗,树突状细胞(dc)是最强大的抗原提呈细胞(apc)之一,它启动和促进抗原特异性细胞毒性T淋巴细胞(如CD8(+) T细胞)的成熟,诱导局部和全身抗肿瘤免疫,进一步抑制肿瘤转移,并产生长期的肿瘤保护作用。因此,dc的激活和成熟是高效的CD8(+) T细胞抗肿瘤免疫应答的先决条件,这被认为是纳米疫苗工程的主要和有前途的任务。在此,我们介绍了一种多用途的纳米疫苗,即用脂粒包被的金纳米笼(lipoos - aunc5)修饰DCs特异性抗体aCD11c,用于靶向递送佐剂MPLA和黑色素瘤抗原肽TRP2,以促进DCs的激活和成熟,并增强肿瘤特异性T淋巴细胞反应。此外,通过体内荧光和光声(PA)成像,可以实时显示AuNCs积累和AuNCs吞噬dc向区域淋巴结(RLNs)的迁移情况,以监测免疫过程。体内实验结果表明,靶向抗原/佐剂负载的aunc在B16-F10预防和肺转移模型中均表现出增强的抗肿瘤免疫应答,抑制肿瘤生长和转移,这可能是抗肿瘤免疫治疗和体内追踪的有前途的纳米平台。(C) 2017 Elsevier Ltd.版权所有。
For nanovaccine-based cancer immunotherapy, dendritic cells (DCs) are one of the most powerful antigen presenting cells (APCs) that initiate and promote the maturation of antigen-specific cytotoxic T lymphocytes (e.g., CD8(+) T cells) to induce the local and systemic antitumor immunity and further suppress the tumor metastasis and produce long-term protection against tumor. Thus, the activation and maturation of DCs is the prerequisite for efficient CD8(+) T cell-based antitumor immune responses, which is considered as a primary and promising task for nanovaccine engineering. Herein, we introduce a versatile nanovaccine of liposomes-coated gold nanocages (Lipos-AuNC5) Modified with DCs specific antibody aCD11c for targeted delivery of adjuvant MPLA and melanoma antigen peptide TRP2 to promote the activation and maturation of DCs, and enhance tumor specific T lymphocytes responses. Moreover, AuNCs accumulation and AuNCs-engulfed DCs migration to regional lymph nodes (RLNs) became realtime visualization through in vivo fluorescence and photoacoustic (PA) imaging to monitor the immunity process. In vivo experimental results demonstrated that the targeted antigen/adjuvants-loaded AuNCs exhibited enhanced antitumor immune response to inhibit tumor growth and metastasis in both B16-F10 prophylactic and lung metastasis models, which may act as a promising nanoplatform for antitumor immunotherapy and in vivo tracking. (C) 2017 Elsevier Ltd. All rights reserved.