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

Shann S. Yu, Cheryl M. Lau, Susan N. Thomas, W. Gray Jerome, David J. Maron, James H. Dickerson, Jeffrey A. Hubbell, Todd D. Giorgio

Research output: Contribution to journalArticle

92 Scopus citations

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.

Original languageEnglish
Pages (from-to)799-813
Number of pages15
JournalInternational Journal of Nanomedicine
Volume7
DOIs
StatePublished - Dec 5 2012
Externally publishedYes

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Keywords

  • Iron oxides
  • Macrophage targeting
  • Opsonization
  • Poly(ethylene glycol) (PEG)
  • Poly(propylene sulfide) (PPS)

ASJC Scopus subject areas

  • Biophysics
  • Bioengineering
  • Biomaterials
  • Organic Chemistry
  • Drug Discovery

Cite this

Yu, S. S., Lau, C. M., Thomas, S. N., Gray Jerome, W., Maron, D. J., Dickerson, J. H., Hubbell, J. A., & Giorgio, T. D. (2012). Size- and charge-dependent non-specific uptake of PEGylated nanoparticles by macrophages. International Journal of Nanomedicine, 7, 799-813. https://doi.org/10.2147/IJN.S28531