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具有膦酸封端聚乙二醇涂层的层状双氢氧化物纳米粒子的胶体稳定性和蛋白质阻抗增强及其药物传递应用。

Enhanced colloidal stability and protein resistance of layered double hydroxide nanoparticles with phosphonic acid-terminated PEG coating for drug delivery.

机构信息

School of Chemical Engineering, University of New South Wales, Sydney, Australia; Australian Centre for NanoMedicine (ACN), University of New South Wales, Sydney, Australia.

School of Chemical Engineering, University of New South Wales, Sydney, Australia.

出版信息

J Colloid Interface Sci. 2018 Jul 1;521:242-251. doi: 10.1016/j.jcis.2018.03.006. Epub 2018 Mar 3.

DOI:10.1016/j.jcis.2018.03.006
PMID:29574343
Abstract

Conjugating nanoparticles with polyethylene glycol (PEG) is a useful strategy to improve the colloidal and biological stability of nanoparticles. However, studies on PEGylation of two-dimensional layered double hydroxide (LDH) nanoparticles are very limited. The present work reported two functionalization approaches to synthesize PEG-conjugated LDH nanoparticles by introducing phosphonic acid terminated PEG before and after LDH aging. The successful PEGylation was confirmed and suggested to be via electrostatic interaction and a ligand exchange process. Different functionalization approaches resulted in different binding types of PEG on/in LDH nanoparticles. The PEG coating maintained the dispersity of LDH nanoparticles in water and saline with the feeding mass ratio of 1:1. Further colloidal stability tests of PEGylated LDHs revealed that the PEGylated LDH dispersity was affected by the feeding mass ratio of PEG/LDH, the molar weight of PEG and anions intercalated in the LDHs. In a test to determine the extent of non-specific protein adsorption, the PEGylation was effective at resisting non-specific bovine serum albumin adsorption on LDH nanoparticles with both functionalization methods investigated. Moreover, PEGylated LDH nanoparticles had no effect on cell viability up to 500 µg/mL, and demonstrated enhanced cellular uptake in a SK-MEL-28 cell culture. The results in this work indicate that conjugating phosphonic acid-terminated PEG on LDH nanoparticles is a promising strategy to improve the colloidal and biological stability of LDHs for biomedical applications.

摘要

通过聚乙二醇(PEG)对纳米颗粒进行偶联是提高纳米颗粒胶体和生物稳定性的有效策略。然而,关于二维层状双氢氧化物(LDH)纳米颗粒的 PEG 化研究非常有限。本工作报道了两种功能化方法,通过在 LDH 老化前后引入末端为磷酸的 PEG 来合成 PEG 接枝的 LDH 纳米颗粒。成功的 PEG 化得到了证实,并被认为是通过静电相互作用和配体交换过程实现的。不同的功能化方法导致 PEG 在 LDH 纳米颗粒上的结合类型不同。PEG 涂层保持了 LDH 纳米颗粒在水和盐水中的分散性,PEG/LDH 的进料质量比为 1:1。进一步对 PEG 化 LDH 的胶体稳定性测试表明,PEG 化 LDH 的分散性受到 PEG/LDH 的进料质量比、PEG 的摩尔质量和 LDH 中插层阴离子的影响。在确定非特异性蛋白质吸附程度的测试中,两种研究的功能化方法都证明 PEG 化可有效抵抗 LDH 纳米颗粒上非特异性牛血清白蛋白的吸附。此外,PEG 化 LDH 纳米颗粒在 500µg/mL 以下对细胞活力没有影响,并在 SK-MEL-28 细胞培养中显示出增强的细胞摄取。本工作的结果表明,在 LDH 纳米颗粒上接枝末端为磷酸的 PEG 是提高 LDH 胶体和生物稳定性用于生物医学应用的一种有前途的策略。

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