Browse by author
Lookup NU author(s): Dr Linping Wu, Professor Moein MoghimiORCiD
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
© 2015 American Chemical Society.Notwithstanding rapid advances of nanotechnology in diagnostic imaging and drug delivery, the engineered nanocarriers still exhibit substantial lack of hemocompatibility. Thus, when injected systemically, nanoparticles are avidly recognized by blood leukocytes and platelets, but the mechanisms of immune recognition are not well understood and strategies to mitigate these phenomena remain underexplored. Using superparamagnetic dextran iron oxide (SPIO) nanoworms (NWs) we demonstrate an efficient and predominantly complement-dependent uptake by mouse lymphocytes, neutrophils and monocytes from normal and tumor bearing mice in vitro. Following intravenous injection into wild type mice, blood leukocytes as well as platelets became magnetically labeled, while the labeling was decreased by 95% in complement C3-deficient mice. Using blood cells from healthy and cancer patient donors, we demonstrated that neutrophils, monocytes, lymphocytes and eosinophils took up SPIO NWs, and the uptake was prevented by EDTA (a general complement inhibitor) and by antiproperdin antibody (an inhibitor of the alternative pathway of the complement system). Cross-linking and hydrogelation of SPIO NWs surface by epichlorohydrin decreased C3 opsonization in mouse serum, and consequently reduced the uptake by mouse leukocytes by more than 70% in vivo. Remarkably, the cross-linked particles did not show a decrease in C3 opsonization in human serum, but showed a significant decrease (over 60%) of the uptake by human leukocytes. The residual uptake of cross-linked nanoparticles was completely blocked by EDTA. These findings demonstrate species differences in complement-mediated nanoparticle recognition and uptake by leukocytes, and further show that human hemocompatibility could be improved by inhibitors of complement alternative pathway and by nanoparticle surface coating. These results provide important insights into the mechanisms of hemocompatibility of nanomedicines.
Author(s): Inturi S, Wang G, Chen F, Banda NK, Holers VM, Wu L, Moghimi SM, Simberg D
Publication type: Article
Publication status: Published
Journal: ACS Nano
Year: 2015
Volume: 9
Issue: 11
Pages: 10758-10768
Print publication date: 24/11/2015
Online publication date: 21/10/2015
Acceptance date: 19/10/2015
ISSN (print): 1936-0851
ISSN (electronic): 1936-086X
Publisher: American Chemical Society
URL: https://doi.org/10.1021/acsnano.5b05061
DOI: 10.1021/acsnano.5b05061
PubMed id: 26488074
Altmetrics provided by Altmetric
