Gold nanoparticle delivery of modified CpG stimulates macrophages and inhibits tumor growth for enhanced immunotherapy.
Gold nanoparticle delivery of modified CpG stimulates macrophages and inhibits tumor growth for enhanced immunotherapy.
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DOI：
10.1371/journal.pone.0063550
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Drezek RA
中科院分区：
文献类型：
--
作者：
Lin AY;Almeida JP;Bear A;Liu N;Luo L;Foster AE;Drezek RA
金纳米粒子在免疫细胞中的积聚通常被视为癌症治疗性给药的一种副作用；然而，这种现象可用于开发金纳米粒子介导的免疫疗法。在此，我们使用一种简单且可扩展的自组装单层方案，将一种修饰的CpG寡脱氧核苷酸免疫刺激剂与金纳米粒子结合，该方案在体外和体内增强了CpG的功能。纳米粒子可通过被动地增强CpG向内源性效应细胞的递送而减轻全身性副作用。在传统的多聚胸腺嘧啶间隔基之上使用三甘醇（TEG）间隔基，在不牺牲纳米粒子上DNA含量的情况下增加了CpG对巨噬细胞的刺激作用，而DNA含量与粒子摄取直接相关。此外，修饰的CpG - 金纳米粒子（CpG - AuNPs）的免疫效应因核心粒子大小而改变，较小的15nm金纳米粒子产生最大的免疫反应。与游离CpG治疗相比，这些TEG修饰的CpG - 金纳米粒子复合物诱导了巨噬细胞和树突状细胞向肿瘤浸润，显著抑制了肿瘤生长，并提高了小鼠的存活率。
Gold nanoparticle accumulation in immune cells has commonly been viewed as a side effect for cancer therapeutic delivery; however, this phenomenon can be utilized for developing gold nanoparticle mediated immunotherapy. Here, we conjugated a modified CpG oligodeoxynucleotide immune stimulant to gold nanoparticles using a simple and scalable self-assembled monolayer scheme that enhanced the functionality of CpG in vitro and in vivo. Nanoparticles can attenuate systemic side effects by enhancing CpG delivery passively to innate effector cells. The use of a triethylene glycol (TEG) spacer on top of the traditional poly-thymidine spacer increased CpG macrophage stimulatory effects without sacrificing DNA content on the nanoparticle, which directly correlates to particle uptake. In addition, the immune effects of modified CpG-AuNPs were altered by the core particle size, with smaller 15 nm AuNPs generating maximum immune response. These TEG modified CpG-AuNP complexes induced macrophage and dendritic cell tumor infiltration, significantly inhibited tumor growth, and promoted survival in mice when compared to treatments with free CpG.
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影响因子：
6.2
作者：
Bode C;Zhao G;Steinhagen F;Kinjo T;Klinman DM
通讯作者：
Klinman DM
影响因子：
6.4
作者：
Behboudi, S;Chao, D;Austyn, J
通讯作者：
Austyn, J
影响因子：
4.4
作者：
Bourquin, Carole;Anz, David;Endres, Stefan
通讯作者：
Endres, Stefan
影响因子：
16.6
作者：
Lee, In-Hyun;Kwon, Ho-Keun;Jon, Sangyong
通讯作者：
Jon, Sangyong
DOI：
10.1073/pnas.1105200108
发表时间：
2011-09-20
影响因子：
11.1
作者：
Jewell, Christopher M.;Lopez, Sandra C. Bustamante;Irvine, Darrell J.
通讯作者：
Irvine, Darrell J.