The Human In Vivo Biomolecule Corona onto PEGylated Liposomes: A Proof-of-Concept Clinical Study

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

The self-assembled layered adsorption of proteins onto nanoparticle (NP) surfaces, once in contact with biological fluids, is termed the "protein corona" and it is gradually seen as a determinant factor for the overall biological behavior of NPs. Here, the previously unreported in vivo protein corona formed in human systemic circulation is described. The human-derived protein corona formed onto PEGylated doxorubicin-encapsulated liposomes (Caelyx) is thoroughly characterized following the recovery of liposomes from the blood circulation of ovarian carcinoma patients. In agreement with previous investigations in mice, the in vivo corona is found to be molecularly richer in comparison to its counterpart ex vivo corona. The intravenously infused liposomes are able to scavenge the blood pool and surface-capture low-molecular-weight, low-abundance plasma proteins that cannot be detected by conventional plasma proteomic analysis. This study describes the previously elusive or postulated formation of protein corona around nanoparticles in vivo in humans and illustrates that it can potentially be used as a novel tool to analyze the blood circulation proteome.

Related collections

Most cited references 29

Record: found
Abstract: not found
Article: not found

Analysis of nanoparticle delivery to tumours

Stefan Wilhelm, Anthony Tavares, Huan-Qin Dai … (2016)

0 comments Cited 1287 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Protein adsorption is required for stealth effect of poly(ethylene glycol)- and poly(phosphoester)-coated nanocarriers

Katharina Landfester, Frederik R. Wurm, Svenja Winzen … (2016)

The current gold standard to reduce non-specific cellular uptake of drug delivery vehicles is by covalent attachment of poly(ethylene glycol) (PEG). It is thought that PEG can reduce protein adsorption and thereby confer a stealth effect. Here, we show that polystyrene nanocarriers that have been modified with PEG or poly(ethyl ethylene phosphate) (PEEP) and exposed to plasma proteins exhibit a low cellular uptake, whereas those not exposed to plasma proteins show high non-specific uptake. Mass spectrometric analysis revealed that exposed nanocarriers formed a protein corona that contains an abundance of clusterin proteins (also known as apolipoprotein J). When the polymer-modified nanocarriers were incubated with clusterin, non-specific cellular uptake could be reduced. Our results show that in addition to reducing protein adsorption, PEG, and now PEEPs, can affect the composition of the protein corona that forms around nanocarriers, and the presence of distinct proteins is necessary to prevent non-specific cellular uptake.

0 comments Cited 331 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

The nanoparticle biomolecule corona: lessons learned - challenge accepted?

D Docter, D Westmeier, M. Markiewicz … (2015)

Besides the wide use of engineered nanomaterials (NMs) in technical products, their applications are not only increasing in biotechnology and biomedicine, but also in the environmental field. While the physico-chemical properties and behaviour of NMs can be characterized accurately under idealized conditions, this is no longer the case in complex physiological or natural environments. Herein, proteins and other biomolecules rapidly bind to NMs, forming a protein/biomolecule corona that critically affects the NMs' (patho)biological and technical identities. As the corona impacts the in vitro and/or in vivo NM applications in humans and ecosystems, a mechanistic understanding of its relevance and of the biophysical forces regulating corona formation is mandatory. Based on recent insights, we here critically review and present an updated concept of corona formation and evolution. We comment on how corona signatures may be linked to effects at the nano-bio interface in physiological and environmental systems. In order to comprehensively analyse corona profiles and to mechanistically understand the coronas' biological/ecological impact, we present a tiered multidisciplinary approach. To stimulate progress in this field, we introduce the potential impact of the corona for NM-microbiome-(human)host interactions and the novel concept of 'nanologicals', i.e., the nanomaterial-specific targeting of molecular machines. We conclude by discussing the relevant challenges that still need to be resolved in this field.

0 comments Cited 163 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Title: Advanced Materials

Abbreviated Title: Adv. Mater.

Publisher: Wiley

ISSN: 09359648

Publication date (Electronic): November 28 2018

Page: 1803335

Affiliations

[1 ]Nanomedicine Lab; Faculty of Biology, Medicine and Health; The University of Manchester; AV Hill Building Manchester M13 9PT UK

[2 ]Manchester Cancer Research Centre Biobank; The Christie NHS Foundation Trust; CRUK Manchester Institute; Manchester M20 4BX UK

[3 ]Institute of Cancer Sciences and The Christie NHS Foundation Trust; Manchester Cancer Research Centre (MCRC); University of Manchester; Manchester M20 4GJ UK

[4 ]Bio-MS Facility; The University of Manchester; Michael Smith Building Manchester M13 9PT UK

[5 ]CRUK Manchester Institute; The University of Manchester; Manchester SK10 4TG UK