Effects of PEGylation on capture of dextran-coated magnetic nanoparticles in microcirculation

Abstract

Background

Magnetic nanoparticles (MNPs) can be localized against hemodynamic forces in blood vessels with the application of an external magnetic field. In addition, PEGylation of nanoparticles may increase the half-life of nanocomposites in circulation. In this work, we examined the effect of PEGylation on the magnetic capture of MNPs in vivo.

Methods

Laser speckle contrast imaging and capillaroscopy were used to assess the magnetic capture of dextran-coated MNPs and red blood cell (RBC) flow in cremaster microvessels of anesthetized rats. Magnetic capture of MNPs in serum flow was visualized with an in vitro circulating system. The effect of PEGylation on MNP-endothelial cell interaction was studied in cultured cells using an iron assay.

Results

In microcirculation through cremaster muscle, magnet-induced retention of 250 nm MNPs was associated with a variable reduction in RBC flow, suggesting a dynamic coupling of hemodynamic and magnetic forces. After magnet removal, faster restoration of flow was observed in PEG(+) than PEG(–) group, which may be attributed to a reduced interaction with vascular endothelium. However, PEGylation appears to be required for magnetic capture of 50 nm MNPs in microvessels, which was associated with increased hydrodynamic diameter to 130±6 nm in serum, but independent of the ς-potential.

Conclusion

These results suggest that PEGylation may enhance magnetic capture of smaller MNPs and dispersion of larger MNPs after magnet removal, which may potentially affect the targeting, pharmacokinetics and therapeutic efficacy.

Keywords:

• polyethylene glycol
• magnetic nanoparticles
• hemodynamics
• microcirculation
• magnetic targeting

Acknowledgments

The work was supported by Ministry of Science and Technology (MOST 107-2311-B-182-002-), Chang Gung Memorial Hospital (CMRPD1E0013; BMRP432). Thanks also goes to Timothy Wiedmann, Department of Pharmaceutics, University of Minnesota for editing this manuscript.

Abbreviation list

APS, ammonium persulfate; DIW, deionized water; ECGS, endothelial cell growth supplement; FBS, fetal bovine serum; HUVEC, human umbilical vein endothelial cells; KSCN, potassium thiocyanate; Mag, magnet; MNPs, magnetic nanoparticles; MNP_cell, cell-associated MNP; PBS, phosphate buffered saline; PEG, polyethylene glycol; RBCs, red blood cells; RES, reticuloendothelial system; ROIs, regions of interest.

Supplementary material

Figure S1 Cremaster muscle preparation of an anesthetized rat. Left cremaster muscle was spread with tension created by suture on a home-made platform. The muscle preparation was then subjected to laser speckle contrast imaging or cappillaroscipy from above.

Disclosure

The authors report no conflicts of interest in this work.