聚乙二醇化
乙二醇
生物结合
纳米颗粒
表面改性
化学
药物输送
PEG比率
纳米技术
点击化学
材料科学
表面工程
化学工程
组合化学
聚乙二醇
有机化学
经济
物理化学
工程类
财务
作者
Isabel Abánades Lázaro,Salame Haddad,Sabrina Sacca,Claudia Orellana‐Tavra,David Fairén-Jiménez,Ross S. Forgan
出处
期刊:Chem
[Elsevier]
日期:2017-04-01
卷期号:2 (4): 561-578
被引量:302
标识
DOI:10.1016/j.chempr.2017.02.005
摘要
The high storage capacities and excellent biocompatibilities of metal-organic frameworks (MOFs) have made them emerging candidates as drug-delivery vectors. Incorporation of surface functionality is a route to enhanced properties, and here we report on a surface-modification procedure—click modulation—that controls their size and surface chemistry. The zirconium terephthalate MOF UiO-66 is (1) synthesized as ∼200 nm nanoparticles coated with functionalized modulators, (2) loaded with cargo, and (3) covalently surface modified with poly(ethylene glycol) (PEG) chains through mild bioconjugate reactions. At pH 7.4, the PEG chains endow the MOF with enhanced stability toward phosphates and overcome the “burst release” phenomenon by blocking interaction with the exterior of the nanoparticles, whereas at pH 5.5, stimuli-responsive drug release is achieved. The mode of cellular internalization is also tuned by nanoparticle surface chemistry, such that PEGylated UiO-66 potentially escapes lysosomal degradation through enhanced caveolae-mediated uptake. This makes it a highly promising vector, as demonstrated for dichloroacetic-acid-loaded materials, which exhibit enhanced cytotoxicity. The versatility of the click modulation protocol will allow a wide range of MOFs to be easily surface functionalized for a number of applications.
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