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Int J Nanomedicine. 2012;7:799-813. doi: 10.2147/IJN.S28531. Epub 2012 Feb 15.

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

Author information

  • 1Department of Biomedical Engineering, Vanderbilt University, Nashville, TN 37235, 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 T(2)-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:

iron oxides; macrophage targeting; opsonization; poly(ethylene glycol) (PEG); poly(propylene sulfide) (PPS)

PMID:
22359457
[PubMed - indexed for MEDLINE]
PMCID:
PMC3284223
Free PMC Article
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