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Cellular trafficking of low molecular weight heparin incorporated in layered double hydroxide nanoparticles in rat vascular smooth muscle cells

Paper ID Volume ID Publish Year Pages File Format Full-Text
7675 559 2011 7 PDF Available
Title
Cellular trafficking of low molecular weight heparin incorporated in layered double hydroxide nanoparticles in rat vascular smooth muscle cells
Abstract

This paper reports a clear elucidation of the pathway for the cellular delivery of layered double hydroxide (LDH) nanoparticles intercalated with anti-restenotic low molecular weight heparin (LMWH). Cellular uptake of LMWH-LDH conjugates into cultured rat vascular smooth muscle cells (SMCs) measured via flow cytometry was more than ten times greater than that of LMWH alone. Confocal and transmission electron microscopy showed LMWH-LDH conjugates taken up by endosomes, then released into the cytoplasm. We propose that LMWH-LDH is taken up via a unique ‘modified endocytic’ pathway, whereby the conjugate is internalized by SMCs in early endosomes, sorted in late endosomes, and quickly released from late endosomes/lysosomes, avoiding degradation. Treatment of cells with LMWH-LDH conjugates suppressed the activation of ERK1/2 in response to foetal calf serum (FCS) for up to 24 h, unlike unconjugated LMWH which had no significant effect at 24 h. Improved understanding of the intracellular pathway of LMWH-LDH nanohybrids in SMC will allow for refinement of design for LDH nanomedicine applications.

Keywords
Layered double hydroxide (LDH); Low molecular weight heparin (LMWH); Rat vascular smooth muscle cells; Nanoparticle; Endocytosis; Mitogen-activated protein kinase (MAPK) Signal transduction
First Page Preview
Cellular trafficking of low molecular weight heparin incorporated in layered double hydroxide nanoparticles in rat vascular smooth muscle cells
Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 32, Issue 29, October 2011, Pages 7234–7240
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering