Synthesis and use of pHEMA microbeads with human EA.hy 926 endothelial cells

Abstract

Cancer has become a major problem in public health and the resulting bone metastases a worsening factor. Facing it, different strategies have been proposed and mechanisms involved in tumor angiogenesis are being studied. Enhanced permeability retention (EPR) effect is a key step in designing new anticancer drugs. We have prepared poly 2-hydroxyethyl methacrylate (pHEMA) microbeads to target human endothelial EA.hy 926 cells, a cell line derived from human umbilical vein endothelial cells. Microbeads were synthesized by emulsion precipitation method and carried positive or negative charges. EA.hy 926 cells were cultured in 24-well plates and microbeads were deposited on cells at various times. Scanning and transmission electron microscopy, flow cytometry, confocal microscopy, and three-dimensional (3D) reconstruction were used to characterize microbeads and their location outside and inside cells. Microbeads were uptaken by endothelial cells with a better internalization for negatively charged microbeads. 3D reconstruction of confocal optical sections clearly evidenced the uptake and internalization of microbeads by endothelial cells. pHEMA microbeads could represent potential drug carrier in tumor model of metastases.

A non-steroidal anti-inflammatory drug (ketoprofen) does not delay β-TCP bone graft healing

“…In this study, microbeads containing Nile red were prepared as a fluorescent tracer for endothelial cells and macrophages. Microbeads can be rapidly trapped by endothelial cells (particularly in the case of rapid angiogenesis) and phagocytosed by macrophages in the stroma of the tissues [19]. This as been recognized as the Enhanced Permeability Retention effect [41,43,44].…”

“…Microbeads of pHEMA labeled with Nile red were prepared according to our previously reported protocol with minor modifications [18,19]. Briefly, microbeads were prepared by an emulsion precipitation method by using the monomer HEMA (2-hydroxyethyl methacrylate).…”

“…4 hours before euthanasia, animals were injected in the ear marginal vein with a saline solution containing 3 X 10 8 microbeads per ml. The 4 hour period was chosen according to a previous study showing that pHEMA microbeads were rapidly internalized by endothelial cells and by in vivo experiments indicating that microbeads were secondarily found in the cytoplasm of macrophages [19]. Then euthanasia was done by injecting an intracardiac overdose of sodium pentobarbital (Dolethal, Vetoquinol, France).…”

Labeling of endothelial cells with magnetic microbeads by angiophagy

“…Larger particles, such as the composite nanoparticles in a polymer shell/carrier, as the commercially-available micron-sized beads used here, would be preferable since a stronger magnetic force (proportional to particle’s mass) can be generated as compared to nano-particles. In this regard, the uptake by EC of hydrogel microspheres (Nguyen et al 2009), microparticles (Terrisse et al 2010) and microbeads (Nyangoga et al 2009) have been reported before. Herein, we tested the labeling of the EC with relatively larger magnetic microbeads.…”

Drug delivery systems: Advanced technologies potentially applicable in personalized treatments

“…Other areas of the biomedical field have been accessed by PHEMA drug carriers, namely cancer treatment [ 91 , 93 ] and neurologic diseases treatment [ 94 ].…”