Transferrin-functionalized nanoparticles lose their targeting capabilities when a biomolecule corona adsorbs on the surface

Salvati, Anna; Pitek, Andrzej S.; Monopoli, Marco P.; Prapainop, Kanlaya; Bombelli, Francesca Baldelli; Hristov, Delyan R.; Kelly, Philip M.; Åberg, Christoffer; Mahon, Eugene; Dawson, Kenneth A.

doi:10.1038/nnano.2012.237

Cited by 1,563 publications

(1,380 citation statements)

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“…More complex nanoparticle design and grafting strategies are probably necessary to ensure that conjugated molecules could be recognised by specific receptors and maintain their biological activity. 32,65 Uptake and Transcytosis of TiO2 Nanoparticles.…”

Section: Uptake and Transcytosis Of Human Serum Albumin And Transferrmentioning

confidence: 99%

“…However, achieving targeting in realistic biological environments is not necessarily straightforward, because interactions with biomolecules in the medium may screen the targeting agent on the nanoparticle surface and thereby cause loss of specificity. 32 Another approach to improve nanoparticle transcytosis is to modify the nanoparticles themselves, such as modification of size, shape, and surface. 33,34 By changing nanoparticle properties and design, the profile of proteins adsorbed to their surfaces from the surrounding environment, such as for instance blood serum, is also changed.…”

Section: Introductionmentioning

confidence: 99%

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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: Uptake and Transcytosis Of Human Serum Albumin And Transferrmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Nanoparticle accumulation and transcytosis in brain endothelial cell layers

et al. 2013

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“…Aggregation is most pronounced in the case of the cationic LPXs, human serum [15][16] . Also, the protein corona can alter the intracellular processing of particles, increasing the fraction that accumulates in the lysosomes 17 .…”

Section: Influence Of Ascites Fluid On the Cellular Uptake Of The Lpxmentioning

confidence: 99%

Disregarded Effect of Biological Fluids in siRNA Delivery: Human Ascites Fluid Severely Restricts Cellular Uptake of Nanoparticles

Dakwar

Braeckmans

Demeester

et al. 2015

ACS Appl. Mater. Interfaces

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“…It is also an important strategy in attempts to negotiate the blood-brain barrier (BBB) to treat central nervous system (CNS) disease [56], as well as for the oral delivery of poorly permeable molecules, including peptides and proteins [57]. There appears to be clinical potential for systemically injected targeted NPs using ligands designed to bind receptors overexpressed on cancer cells or on the BBB [58,59], but there is a recognition issue caused by opsoninbased coronas depositing on the surfaces of targeted NPs in the circulation [60]. There is also a growing focus on local targeted delivery of NPs to disease sites that would overcome some of these issues for specific therapeutic needs, such as nebulization to the respiratory tract [61] and implantation within tissue engineering scaffolds [62], Therefore, with myriad organic and inorganic NP constructs emerging, it is important to systematically compare the cytotoxicity of families of (untargeted) NPs to examine the mechanistic basis of lethal and sublethal events in specific cell types following acute and chronic exposure.…”

Section: Hca: Cytotoxicity Of Npsmentioning

confidence: 99%

High-content analysis for drug delivery and nanoparticle applications

Brayden

Cryan

Dawson

et al. 2015

Drug Discovery Today

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Publication information Drug Discovery Today, 20 (8): 942-957Publisher Elsevier Item record/more information http://hdl.handle.net/10197/6636 Publisher's statementThis is the author's version of a work that was accepted for publication in Drug Discovery Today. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Drug Discovery Today, 20 (8), (2015 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Page 1 of 26A c c e p t e d M a n u s c r i p t Sally-Ann CryanSally-Ann Cryan has a pharmacy degree and a PhD in pharmaceutics ( Jeremy SimpsonJeremy Simpson carried out his PhD at the University of Warwick, followed postdoctoral work at the Scripps Research Institute in San Diego, and the Imperial Cancer Research Fund in London. After 9 years as a staff member at the European Molecular Biology Laboratory (EMBL) in Heidelberg (Germany), he was appointed as professor of cell biology at UCD, in 2008. He currently applies high-throughput imaging technologies to study subcellular transport pathways and the internalization routes taken by nanoparticles in cells. He runs the UCD Cell Screening Laboratory and is the author of more than 80 publications.High-content analysis (HCA) provides quantitative multiparametric cellular fluorescence data. From its origins in discovery toxicology, it is now addressing fundamental questions in drug delivery. Nanoparticles (NPs), polymers, and intestinal permeation enhancers are being harnessed in drug delivery systems to modulate plasma membrane properties and the intracellular environment. Identifying comparative mechanistic cytotoxicity on sublethal events is crucial to expedite the development of such systems. NP uptake and intracellular routing pathways are also being dissected using chemical and genetic perturbations, with the potential to assess the intracellular fate of targeted and untargeted particles in vitro. As we discuss here, HCA is set to make a major impact in preclinical delivery research by elucidating the intracellular pathways of NPs and the in vitro mechanistic-based toxicology of formulation constituents. A brief recap of cytotoxicity assaysIn vitro cell-based assays have long been used to assess the cytotoxic effects of drug exposure [1]. Cells undergoing acute necrosis swell and lose metabolic capacity, thereby losing the capacity to maintain a barrier to the extracellular space and the ability ...

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Transferrin-functionalized nanoparticles lose their targeting capabilities when a biomolecule corona adsorbs on the surface

Cited by 1,563 publications

References 36 publications

Nanoparticle accumulation and transcytosis in brain endothelial cell layers

Nanoparticle accumulation and transcytosis in brain endothelial cell layers

Disregarded Effect of Biological Fluids in siRNA Delivery: Human Ascites Fluid Severely Restricts Cellular Uptake of Nanoparticles

High-content analysis for drug delivery and nanoparticle applications

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