<p>Effects of PEGylation on capture of dextran-coated magnetic nanoparticles in microcirculation</p>

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.

Biomimetic Magnetoliposomes as Oxaliplatin Nanocarriers: In Vitro Study for Potential Application in Colon Cancer

“…Only IML pegylation induced a slight increase on their hemolysis capacity (1% to~2%), although within the normal range of hemolysis that is considered biocompatible (0-2%) [47]. Our results are in agreement with the findings of other authors, who documented that pegylation reduced blood proteins binding [48] such as BSA and IgG [49] improving the dispersibility of the nanoparticles and reducing their interactions [50]. On the other hand, pegylation also significantly reduce the interaction between the nanoformulations and the reticuloendothelial system cells such as lymphocytes and macrophages [49,51].…”

“…In terms of cell internalization, it is well documented that SPIONs can accumulate in large amounts inside the cell, both in cancer cells and in normal cells [61,62]. Our hypothesis is that the coating and functionalization of the nanoformulations increase their hydrophilicity and therefore their dispersion [63], and reduce the interactions between particles [50], allowing a greater number of nanoformulations to be available for cell internalization, which previously remained agglutinated. A greater amount of NPs (and thus, also iron) inside the cell increases migration capacity.…”

Cyclic Strain Mitigates Nanoparticle Internalization by Vascular Smooth Muscle Cells

“… 38 , 39 In the presence of plasma proteins as in the culture medium, positive or negative ζ-potentials of nanoparticles tend to become sheltered, which may contribute to further increase in the size of the aggregates. 40 Our results are consistent with previous findings that PLL-MNPs with positive or negative ζ-potentials exhibited similar pattern of interaction with glioma cells in culture. 31 …”

Targeted Delivery of Plasminogen Activators for Thrombolytic Therapy: An Integrative Evaluation

“…Application of magnetic field gradient may capture or manipulate MNPs, allowing “magnetic targeting” in drug delivery. In preclinical studies, simply using an NdFeB magnet may generate magnetic force enough to drag MNPs in circulation against hemodynamic forces in bigger artery with an emboli [24] or microvessels [25]. A magnetic field strength of 0.24 to 0.44 T has been used in animal models to induce magnetic targeting [24,26].…”