Selective Surface PEGylation of UiO-66 Nanoparticles for Enhanced Stability, Cell Uptake, and pH-Responsive Drug Delivery

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 modulati...

Full description

Saved in:
Bibliographic Details
Published in:Chem 2017-04, Vol.2 (4), p.561-578
Main Authors: Abánades Lázaro, Isabel, Haddad, Salame, Sacca, Sabrina, Orellana-Tavra, Claudia, Fairen-Jimenez, David, Forgan, Ross S.
Format: Article
Language:English
Subjects:
drug delivery
endocytosis
metal-organic frameworks
microporous materials
nanoparticles
SDG3: Good health and well-being
surface modification
zirconium
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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. [Display omitted] •A surface modification protocol for MOFs compatible with cargo loading is reported•PEGylated UiO-66 nanoparticles show pH-responsive cargo release•Endocytosis routes are modified by the control of MOF surface chemistry•Enhanced cytotoxicity is observed for PEGylated UiO-66 loaded with dichloroacetate Using artificial agents to deliver drugs selectively to sites of disease while protecting them from metabolism and clearance offers potential routes to new treatments. Porous metal-organic frameworks (MOFs) have emerged as potential candidates because they offer high storage capacities and easy clearance after delivery. We report on a method that controls the size and surface chemistry of MOFs and is compatible with cargo loading, showing that surface modification with biocompatible poly(ethylene glycol) chains improves stability toward phosphate and allows pH-responsive cargo release, which could enhance selectivity because cancerous cells are typically more acidic than healthy ones. Modes of cellular uptake are also altered, which could account for the enhanced cell death when polymer-coated MOFs are loaded with the antic
ISSN:2451-9294
2451-9294
DOI:10.1016/j.chempr.2017.02.005