Uptake and permeability studies of BBB-targeting immunoliposomes using the hCMEC/D3 cell line

Markoutsa, Eleni; Pampalakis, Georgios; Niarakis, Anna; Romero, Ignacio A.; Weksler, Babette B.; Couraud, Pierre‐Olivier; Antimisiaris, Sophia G.

doi:10.1016/j.ejpb.2010.11.015

Cited by 109 publications

(93 citation statements)

References 41 publications

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“…42 Thus, hCMEC/D3 BBB models are an excellent candidate for blood-brain barrier function and transport studies. This human BBB model has been already widely utilized to test the delivery of neurotherapeutic molecules 43 and to study brain signalling mechanisms. 44,45 In this work, we studied the fate of various types of nano-sized materials accessing the blood brain barrier, and we used the hCMEC/D3 cells as an in vitro BBB model for nanoparticle screening.…”

Section: Introductionmentioning

confidence: 99%

Nanoparticle accumulation and transcytosis in brain endothelial cell layers

et al. 2013

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The Blood-Brain Barrier (BBB) is a selective barrier, which controls and limits access to the central nervous system (CNS). The selectivity of the BBB relies on specialized characteristics of the endothelial cells that line the microvasculature, including the expression of intercellular tight junctions, which limit paracellular permeability. Several reports suggest that nanoparticles have a unique capacity to cross the BBB. However, direct evidence of nanoparticle transcytosis is difficult to obtain, and we found that typical transport studies present several limitations when applied to nanoparticles. In order to investigate the capacity of nanoparticles to access and transport across the BBB, several different nanomaterials, including silica, titania and albumin-or transferrinconjugated gold nanoparticles of different sizes, were exposed to a human in vitro BBB model of endothelial hCMEC/D3 cells. Extensive transmission electron microscopy imaging was applied in order to describe nanoparticle endocytosis and typical intracellular localisation, as well as to look for evidence of eventual transcytosis. Our results show that all of the nanoparticles were internalised, to different extents, by the BBB model and accumulated along the endo-lysosomal pathway. Rare events suggestive of nanoparticle transcytosis were also observed for several of the tested materials.

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Section: Introductionmentioning

confidence: 99%

Nanoparticle accumulation and transcytosis in brain endothelial cell layers

et al. 2013

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“…Markoutsa et al investigated the targeting potential of OX-26-decorated immunoliposomes, using the human brain endothelial cell line hCMEC/D3 as a model of BBB. Results showed the uptake and transcytosis of immunoliposome-associated dyes by cell monolayers was substantially higher compared to those of control liposomes (Markoutsa et al 2011). To improve drug transport across the BBB, Du et al developed a kind of dual-targeting topotecan liposomes modified with tamoxifen and wheat germ agglutinin (Du et al 2009).…”

Section: Targeting Physiological Barriersmentioning

confidence: 97%

Advances in investigations on the mechanism of cancer multidrug resistance and the liposomes-based treatment strategy

Zeng

et al. 2014

Journal of Pharmaceutical Investigation

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Multidrug resistance is a major cause that leads to the refractory of cancers after a combination strategy by chemotherapy, radiation and surgical treatment. Among the comprehensive treatment, chemotherapy still plays a crucial role in eliminating malignant cells. The objectives of present review were to elucidate the research advances in the mechanism of cancer multidrug resistance and the liposomes-based treatment strategy. The drug resistance could be related to cancer cells, heterogeneity, microenvironment, and physiological barriers. Drug resistance mechanisms, which involved in adenosine triphosphate (ATP)-binding cassette (ABC) transporters, cytoplasm, nucleus, apoptotic proteins, cancer stem cells, side-population cancer cells, angiogenesis, vasculogenic mimicry channels, extracellular matrix, and blood-brain barrier, were discussed. Latest advances in the nanostructured liposome treatment strategy were summarized, including regulating the overexpression of ABC transporters, and targeting treatments on mitochondria, apoptotic genes, cancer stem cells, cancer side-population cells, new blood vessels, vascular mimicry channels, extracellular matrix, and blood-brain barrier. These translational investigations provide new insights into current cancer therapy, and useful considerations for further developments of the liposomes-based treatment strategy.

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“…The nanoliposome crosses the BBB by one of three methods: passive diffusion, endocytosis, or assisted passage with brain-targeting ligands (Beduneau et al 2007;Chen et al 2010;Markoutsa et al 2011;Tamaru et al 2010;Wong et al 2010). These advanced methods for CNS drug delivery transduce BBB for a particular therapy, but they are not readily tissueselective or cell type-selective.…”

Section: Methods For Transducing the Blood-brain Barriermentioning

confidence: 99%