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

Author:
Liang, Ruijing, Xie, Jun, Li, Jun, Wang, Ke, Liu, Liping, Gao, Yujie, Hussain, Mubashir, Shen, Guanxin, Zhu, Jintao, Tao, Juan
Source:
Biomaterials 2017 v.149 pp. 41-50
ISSN:
0142-9612
Subject:
antibodies, cytotoxic T-lymphocytes, dendritic cells, engineering, fluorescence, gold, image analysis, immune response, immunotherapy, liposomes (artificial), lungs, lymph nodes, melanoma-specific antigens, metastasis, models, nanogold, neoplasms, vaccine adjuvants
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.
Agid:
5837838