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载有抗原和佐剂的脂质体包覆的金纳米笼靶向递送至树突状细胞,增强抗肿瘤免疫反应。

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

机构信息

School of Chemistry and Chemical Engineering, National Engineering Center for Nanomedicine, Huazhong University of Science and Technology (HUST), Wuhan, 430074, China.

School of Chemistry and Chemical Engineering, National Engineering Center for Nanomedicine, Huazhong University of Science and Technology (HUST), Wuhan, 430074, China; Department of Dermatology, Union Hospital, Tongji Medical College, HUST, Wuhan, 430022, China.

出版信息

Biomaterials. 2017 Dec;149:41-50. doi: 10.1016/j.biomaterials.2017.09.029. Epub 2017 Sep 26.

DOI:10.1016/j.biomaterials.2017.09.029
PMID:28992509
Abstract

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-AuNCs) 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 real-time 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.

摘要

对于基于纳米疫苗的癌症免疫疗法,树突状细胞 (DCs) 是最强大的抗原提呈细胞 (APCs) 之一,它可以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,从而诱导局部和全身抗肿瘤免疫,并进一步抑制肿瘤转移,产生对肿瘤的长期保护。因此,DCs 的激活和成熟是有效基于 CD8 T 细胞抗肿瘤免疫反应的前提,这被认为是纳米疫苗工程的首要和有前途的任务。在此,我们介绍了一种多功能的纳米疫苗,即负载有 DC 特异性抗体 aCD11c 的脂质体包覆的金纳米笼 (Lipos-AuNCs),用于靶向递送至佐剂 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 淋巴细胞的反应。此外,通过体内荧光和光声 (PA) 成像进行实时可视化,可以监测 AuNCs 的积累和 AuNCs 吞噬的 DCs 向区域淋巴结 (RLNs) 的迁移,以监测免疫过程。体内实验结果表明,靶向抗原/佐剂负载的 AuNCs 表现出增强的抗肿瘤免疫反应,可抑制 B16-F10 预防性和肺转移模型中的肿瘤生长和转移,这可能作为一种有前途的抗肿瘤免疫治疗和体内追踪的纳米平台。

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