Oxidized Multiwalled Carbon Nanotubes as Antigen Delivery System to Promote Superior CD8+ T Cell Response and Protection against Cancer
Oxidized Multiwalled Carbon Nanotubes as Antigen Delivery System to Promote Superior CD8+ T Cell Response and Protection against Cancer
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DOI：
10.1021/nl502911a
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发表时间：
2014-09-01
期刊：
影响因子：
10.8
通讯作者：
Gazzinelli, Ricardo Tostes
中科院分区：
文献类型：
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作者：
Batista de Faria, Paula Cristina;dos Santos, Luara Isabela;Gazzinelli, Ricardo Tostes
碳纳米管（CNTs）具有与细胞膜的高界面面积、结合多种功能化的独特能力以及在生物流体中的相容性和运输等特性，可用于各种治疗和药物输送应用。在这里，我们使用一种完全合成的杂交超分子作为抗癌疫苗配方。该复杂结构包括CNTs作为睾丸癌抗原NY-ESO-1的递送系统，与合成toll样受体激动剂结合。在体外和体内，碳纳米管结构被迅速内化到树突状细胞中，并作为细胞内抗原仓库。这一特性有利于诱导强CD4(+) T和CD8(+) T细胞介导的针对NY-ESO-1的免疫应答。重要的是，疫苗接种显著延缓了肿瘤的发展并延长了小鼠的生存期，这突出了CNTs作为疫苗递送系统提供优越的免疫原性和强大的抗癌保护的潜在应用
Properties like high interfacial area with cellular membranes, unique ability to incorporate multiple functionalization, as well as compatibility and transport in biological fluids make carbon nanotubes (CNTs) useful for a variety of therapeutic and drug-delivery applications. Here we used a totally synthetic hybrid supramolecule as an anticancer vaccine formulation. This complex structure comprises CNTs as delivery system for the Cancer Testis Antigen named NY-ESO-1, allied to a synthetic Toll-Like Receptor agonist. The CNT constructs were rapidly internalized into dendritic cells, both in vitro and in vivo, and served as an intracellular antigen depot. This property favored the induction of strong CD4(+) T as well as CD8(+) T cell-mediated immune responses against the NY-ESO-1. Importantly, the vaccination significantly delayed the tumor development and prolonged the mice survival, highlighting the potential application of CNTs as a vaccine delivery system to provide superior immunogenicity and strong protection against cancer