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一种稳健的接枝策略,用于形成多功能和隐形两性离子聚合物涂层的介孔硅纳米粒子。

A robust graft-to strategy to form multifunctional and stealth zwitterionic polymer-coated mesoporous silica nanoparticles.

机构信息

Department of Chemical Engineering, University of Washington , Seattle, Washington 98195, United States.

出版信息

Biomacromolecules. 2014 May 12;15(5):1845-51. doi: 10.1021/bm500209a. Epub 2014 Apr 8.

DOI:10.1021/bm500209a
PMID:24670217
Abstract

Mesoporous silica nanoparticles (MSNs) are a new class of carrier materials promising for drug/gene delivery and many other important applications. Stealth coatings are necessary to maintain their stability in complex media. Herein, a biomimetic polymer conjugate containing one ultralow fouling poly(carboxybetaine) (pCBMA) chain and one surface-adhesive catechol (DOPA) residue group was efficiently grafted to the outer surface of SBA-15 type MSNs using a convenient and robust method. The cytotoxicity of SBA-15-DOPA-pCBMAs was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Results showed no significant decrease in cell viability at the tested concentration range. Macrophage cell uptake studies revealed that the uptake ratios of SBA-15-DOPA-pCBMAs were much lower than that of parent MSNs. Furthermore, inductively coupled plasma mass spectrometry (ICP-MS) analysis results showed that after SBA-15-DOPA-pCBMAs were conjugated with a targeting cyclo-[Arg-Gly-Asp-d-Tyr-Lys] (cRGD) peptide, uptake by bovine aortic endothelial cells (BAECs) was notably increased. Results indicated that cRGD-functionalized MSNs were able to selectively interact with cells expressing αvβ3 integrin. Thus, MSNs with DOPA-pCBMAs are promising as stealth multifunctional biocarriers for targeted drug delivery or diagnostics.

摘要

介孔硅纳米颗粒(MSNs)是一类有前途的药物/基因传递载体材料,在许多其他重要应用中也有应用。为了保持其在复杂介质中的稳定性,需要进行隐形涂层。本文采用一种简便、稳健的方法,将含有一条超低抗污聚(羧基甜菜碱)(pCBMA)链和一条表面黏附儿茶酚(DOPA)残基的仿生聚合物偶联物有效地接枝到 SBA-15 型 MSNs 的外表面。通过 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐(MTT)测定法评估了 SBA-15-DOPA-pCBMAs 的细胞毒性。结果表明,在测试浓度范围内,细胞活力没有明显下降。巨噬细胞摄取研究表明,SBA-15-DOPA-pCBMAs 的摄取率远低于母体 MSNs。此外,电感耦合等离子体质谱(ICP-MS)分析结果表明,SBA-15-DOPA-pCBMAs 与靶向环-[精氨酸-甘氨酸-天冬氨酸-酪氨酰-赖氨酰](cRGD)肽偶联后,牛主动脉内皮细胞(BAECs)的摄取量明显增加。结果表明,cRGD 功能化的 MSNs 能够与表达αvβ3 整合素的细胞选择性相互作用。因此,具有 DOPA-pCBMAs 的 MSNs 有望成为用于靶向药物传递或诊断的隐形多功能生物载体。

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