Imageable Antigen-Presenting Gold Nanoparticle Vaccines for Effective Cancer Immunotherapy In Vivo
Imageable Antigen-Presenting Gold Nanoparticle Vaccines for Effective Cancer Immunotherapy In Vivo
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DOI：
10.1002/anie.201203193
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发表时间：
2012-01-01
影响因子：
16.6
通讯作者：
Jon, Sangyong
中科院分区：
文献类型：
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作者：
Lee, In-Hyun;Kwon, Ho-Keun;Jon, Sangyong
在佐剂的帮助下接种疫苗是预防各种疾病的一种非常有效的治疗选择然而，研制针对现有癌症和慢性病毒性疾病（如丙型肝炎和艾滋病毒）的疫苗已被证明是困难的，这在很大程度上是因为无法诱导协调一致和有效的体液和细胞免疫为了克服这一问题，人们在开发治疗性癌症疫苗的新技术方面付出了很多努力，这些疫苗能够长期诱导强的、抗原特异性的CD8+ t细胞，并诱导对现有肿瘤的抗体反应发展这种技术的一个关键考虑因素是如何实现抗原向抗原呈递细胞（APCs）的有效递送，随后激活和成熟细胞，最大限度地交叉呈递，诱导细胞毒性CD8+ T细胞反应从这个意义上说，将疫苗递送到局部淋巴结（LN）可能是一种合适的策略，因为淋巴结可能含有大量的apc（例如，常驻树突状细胞、浆细胞样树突状细胞和巨噬细胞）以及负责体液和细胞免疫的免疫细胞为此，天然或合成的纳米颗粒已成为抗原递送的潜在候选者，因为它们可以通过淋巴管以大小依赖的方式有效地递送到LNs。[5b， 7]重要的是，较小的纳米颗粒（直径约为25 nm）在局部LN中的累积量明显大于约100 nm大小的大纳米颗粒。[5b]在设计针对LNs的纳米颗粒疫苗时，有四个关键考虑因素：1)为了有效递送，颗粒直径应低于50 nm；2)抗原和/或佐剂应该是多功能的，并且易于与纳米颗粒相适应；3)疫苗内化后，必须适当激活apc，以促进诱导体液和细胞免疫；4)如果疫苗是可追溯的，以无创的方式来预测疗效是有益的。由于以下原因，金纳米颗粒（AuNPs）可能是最适合的纳米颗粒之一。首先，易于控制AuNPs的大小，其范围从大约1nm到几百nm不等。其次，多种分子物种，包括蛋白质、[8]肽、[9]和寡核苷酸、[10]，可以通过简单的化学方法很容易地附着在AuNPs的表面。第三，aunp具有生物相容性和无毒性。[8b， d]第四，可以使用计算机断层扫描（CT）成像来跟踪aunp，这在几乎所有医院都很容易获得。[10,11]考虑到这些因素，本文首次报道了基于aunp的癌症疫苗，该疫苗能够有效地将抗原递送到靶LNs，使用无创临床成像跟踪疫苗，并有效地预防和治疗癌症。
Vaccination with the aid of adjuvants is a highly effective therapeutic option for the prevention of various diseases.[1] However, development of vaccines against existing cancers and chronic viral diseases, such as hepatitis C and HIV, has proved difficult owing in large part to an inability to induce concerted and potent humoral and cellular immunity.[2] With the aim of overcoming this problem, much effort has gone into developing novel technologies for therapeutic cancer vaccines that enable long-lasting induction of strong, antigenspecific CD8+ Tcells, as well as induction of antibody responses to existing tumors.[3] A key consideration in developing such technology is how to achieve efficient antigen delivery to antigen-presenting cells (APCs) with subsequent activation and maturation of cells that maximize cross-presentation for inducing cytotoxic CD8+ T cell responses.[4] In that sense, vaccine delivery to a local lymph node (LN) might be an appropriate strategy, because the node would contain a high population of APCs (eg, resident dendritic cells, plasmacytoid dendritic cells, and macrophages) along with immune cells responsible for both humoral and cellular immunity.[5] To that end, nanoparticles of natural or synthetic origin have emerged as potential candidates for antigen delivery,[6] since they can be efficiently delivered to LNs through lymphatic vessels in a size-dependent manner.[5b, 7] Importantly, smaller nanoparticles (ca. 25 nm in diameter) could lead to significantly larger accumulation in a local LN than larger nanoparticles of approximately 100 nm in size.[5b]There are four key considerations when designing a nanoparticulate vaccine for targeting LNs: 1) for efficient delivery, the particle diameter should be below 50 nm; 2) the antigens and/or adjuvants should be versatile and easily accommodated to the nanoparticles; 3) after internalization, the vaccine must properly activate APCs to facilitate induction of humoral and cellular immunity; and 4) it is beneficial if the vaccine is traceable in a noninvasive manner to predict efficacy. For the following reasons, gold nanoparticles (AuNPs) may be one of the most suitable nanoparticles for the purpose. First, it is easy to control the size of AuNPs, which can range from approximately 1 nm to several hundred nm. Second, a variety of molecular species, including proteins,[8] peptides,[9] and oligonucleotides,[10] can be easily attached to the surface of AuNPs using simple chemistry. Third, AuNPs are biocompatible and nontoxic.[8b, d] Fourth, AuNPs can be tracked using computed tomography (CT) imaging, which is readily available at nearly all hospitals.[10, 11] With these considerations in mind, herein we, for the first time, report AuNP-based cancer vaccines that enable efficient delivery of an antigen to target LNs, tracking of the vaccines using noninvasive clinical imaging, and effective cancer prevention and therapy.