Simultaneous Cross-Linking and Cross-Polymerization of Enzyme Responsive Polyethylene Glycol Nanogels in Confined Aqueous Droplets for Reduction of Low-Density Lipoprotein Oxidation
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Simultaneous Cross-Linking and Cross-Polymerization of Enzyme Responsive Polyethylene Glycol Nanogels in Confined Aqueous Droplets for Reduction of Low-Density Lipoprotein Oxidation. / Basak, Suman; Khare, Harshvardhan Ajay; Roursgaard, Martin; Kempen, Paul J.; Lee, Jong Hyun; Bazban-Shotorbani, Salime; Kraemer, Martin; Chernyy, Sergey; Andresen, Thomas L.; Almdal, Kristoffer; Kamaly, Nazila.
In: Biomacromolecules, Vol. 22, No. 2, 2021, p. 386-398.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Simultaneous Cross-Linking and Cross-Polymerization of Enzyme Responsive Polyethylene Glycol Nanogels in Confined Aqueous Droplets for Reduction of Low-Density Lipoprotein Oxidation
AU - Basak, Suman
AU - Khare, Harshvardhan Ajay
AU - Roursgaard, Martin
AU - Kempen, Paul J.
AU - Lee, Jong Hyun
AU - Bazban-Shotorbani, Salime
AU - Kraemer, Martin
AU - Chernyy, Sergey
AU - Andresen, Thomas L.
AU - Almdal, Kristoffer
AU - Kamaly, Nazila
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
U2 - 10.1021/acs.biomac.0c01238
DO - 10.1021/acs.biomac.0c01238
M3 - Journal article
C2 - 33125232
VL - 22
SP - 386
EP - 398
JO - Biomacromolecules
JF - Biomacromolecules
SN - 1525-7797
IS - 2
ER -
ID: 258622420