Simultaneous Cross-Linking and Cross-Polymerization of Enzyme Responsive Polyethylene Glycol Nanogels in Confined Aqueous Droplets for Reduction of Low-Density Lipoprotein Oxidation

Suman Basak, Harshvardhan Ajay Khare, Martin Roursgaard, Paul Kempen, Jong Hyun Lee, Salime Bazban-Shotorbani, Martin Kræmer, Sergey Chernyy, Thomas Lars Andresen, Kristoffer Almdal, Nazila Kamaly*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

A key initiating step in atherosclerosis is the accumulation and retention of apolipoprotein B complexing lipoproteins within the artery walls. In this work, we address this exact initiating mechanism of atherosclerosis, which results from the oxidation of low-density lipoproteins (oxLDL) using therapeutic nanogels. We present the development of biocompatible polyethylene glycol (PEG) cross-linked nanogels formed from a single simultaneous cross-linking and co-polymerization step in water without the requirement for an organic solvent, high temperature, or shear stress. The nanogel synthesis also incorporates in situ noncovalent electrostatically driven template polymerization around an innate anti-inflammatory and anti-oxidizing paraoxonase-1 (PON-1) enzyme payload-the release of which is triggered because of matrix metalloproteinase responsive elements instilled in the PEG cross-linker monomer. The results obtained demonstrate the potential of triggered release of the PON-1 enzyme and its efficacy against the production of ox-LDL, and therefore a reduction in macrophage foam cell and reactive oxygen species formation.

Original languageEnglish
JournalBiomacromolecules
ISSN1525-7797
DOIs
Publication statusAccepted/In press - 2020

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