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Size- and charge-dependent non-specific uptake of PEGylated nanoparticles by macrophages

Authors Yu SS, Lau CM, Thomas SN, Jerome WG, Maron DJ, Dickerson JH, Hubbell JA, Giorgio TD

Received 23 November 2011

Accepted for publication 29 December 2011

Published 15 February 2012 Volume 2012:7 Pages 799—813

DOI https://doi.org/10.2147/IJN.S28531

Review by Single-blind

Peer reviewer comments 4

Shann S Yu1,2, Cheryl M Lau1, Susan N Thomas3, W Gray Jerome4, David J Maron5, James H Dickerson2,6, Jeffrey A Hubbell3, Todd D Giorgio1,2,7,8

1Department of Biomedical Engineering, Vanderbilt University, Nashville, 2Vanderbilt Institute of Nanoscale Science and Engineering, Nashville, TN, USA; 3Institute of Bioengineering, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland, 4Department of Pathology, Vanderbilt University Medical Center, Nashville, 5Vanderbilt Heart and Vascular Institute, Nashville, 6Department of Physics and Astronomy, Vanderbilt University, Nashville, 7Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, 8Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USA

Abstract: The assessment of macrophage response to nanoparticles is a central component in the evaluation of new nanoparticle designs for future in vivo application. This work investigates which feature, nanoparticle size or charge, is more predictive of non-specific uptake of nanoparticles by macrophages. This was investigated by synthesizing a library of polymer-coated iron oxide micelles, spanning a range of 30–100 nm in diameter and -23 mV to +9 mV, and measuring internalization into macrophages in vitro. Nanoparticle size and charge both contributed towards non-specific uptake, but within the ranges investigated, size appears to be a more dominant predictor of uptake. Based on these results, a protease-responsive nanoparticle was synthesized, displaying a matrix metalloproteinase-9 (MMP-9)-cleavable polymeric corona. These nanoparticles are able to respond to MMP-9 activity through the shedding of 10–20 nm of hydrodynamic diameter. This MMP-9-triggered decrease in nanoparticle size also led to up to a six-fold decrease in nanoparticle internalization by macrophages and is observable by T2-weighted magnetic resonance imaging. These findings guide the design of imaging or therapeutic nanoparticles for in vivo targeting of macrophage activity in pathologic states.

Keywords: macrophage targeting, poly(ethylene glycol) (PEG), poly(propylene sulfide) (PPS), iron oxides, opsonization

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