Gold nanoparticles coated with polysarcosine brushes to enhance their colloidal stability and circulation time in vivo

Gold nanoparticles coated with polysarcosine brushes to enhance their colloidal stability and circulation time in vivo
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DOI:
10.1016/j.jcis.2016.08.038
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发表时间:
2016-12-01
影响因子:
9.9
通讯作者:
Ling, Jun
Ling, Jun
中科院分区:
化学1区
文献类型:
--
作者:
Chen, Ying;Xu, Zhengqing;Ling, Jun

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多糖肌氨酸(Polysarcosine,PS)是一种结构类似多肽的非离子型亲水类多肽,具有天然氨基酸重复单元,由于其良好的亲水性和生物相容性,已被用于稳定金纳米粒子(AuNPs)。合成了具有不同分子量的二硫键官能化的聚肌氨酸,并通过传统的配体交换将其用于封端金纳米粒子。通过傅里叶变换红外光谱(FTIR)和表面zeta电位的变化证明了PS在AuNPs上的接枝。聚肌氨酸包被的金纳米粒子(Au@PS)在较宽的pH范围和盐溶液中具有良好的稳定性。它们对二硫苏糖醇(DTT)的配体竞争具有较强的抗性。它们在血清中表现出良好的稳定性,与蛋白质具有分子量依赖性的相互作用模式。Au@PS在体外具有非常低的细胞毒性和细胞摄取。根据体外试验结果,选择稳定金纳米颗粒能力最强的分子量为5 kD的聚肌氨酸进行体内试验。静脉注射后,Au@PS在血液中的循环时间比Au@PEG长,表明聚肌氨酸具有更好的类隐形性质。Au@PS在体内未引起明显毒性,提示其在疾病诊断和治疗中具有潜在的应用价值。(C)2016 Elsevier Inc. All rights reserved.
Polysarcosine (PS), a non-ionic hydrophilic polypeptoid whose structure is similar to polypeptides, bearing repeating units of natural alpha-amino acid, has been used to stabilize gold nanoparticles (AuNPs) due to its excellent hydrophilicity and biocompatibility. Disulfide functionalized polysarcosines with different molecular weight were synthesized and used to cap AuNPs by traditional ligand exchange. The grafting of PS on AuNPs was evidenced by Fourier transform infrared (FTIR) spectroscopy and the alternation of surface zeta potential. The polysarcosine coated AuNPs (Au@PS) showed good stabilities in wide pH range and saline condition. They had strong resistance to ligand competition of dithiothreitol (DTT). They showed good stability in serum, with a molecular weight dependent interaction pattern with proteins. The Au@PS had very low cytotoxicity and cell uptake in vitro. Based on the results in vitro, polysarcosine with molecular weight of 5 kD with the best ability to stabilize AuNPs was used for in vivo test. The Au@PS had a longer circulation time in blood after intravenous injection than that of Au@PEG, indicating a better stealth-like property of polysarcosine. The Au@PS did not cause obvious toxicity in vivo, suggesting potential applications in disease diagnosis and therapy. (C) 2016 Elsevier Inc. All rights reserved.