Nanomedicine: Evolution of the nanoparticle corona.
TL;DR: Understanding how complement proteins bind to nanoparticles and participate in their surface 'corona' can provide further insight into the relevance of the protein corona concept in medicine.
Abstract: Understanding how complement proteins bind to nanoparticles and participate in their surface 'corona' can provide further insight into the relevance of the protein corona concept in medicine.
Citations
More filters
TL;DR: A ‘minimum information standard’ for experimental literature investigating bio–nano interactions is suggested, consisting of specific components to be reported, divided into three categories: material characterization, biological characterization and details of experimental protocols.
Abstract: Studying the interactions between nanoengineered materials and biological systems plays a vital role in the development of biological applications of nanotechnology and the improvement of our fundamental understanding of the bio-nano interface. A significant barrier to progress in this multidisciplinary area is the variability of published literature with regards to characterizations performed and experimental details reported. Here, we suggest a 'minimum information standard' for experimental literature investigating bio-nano interactions. This standard consists of specific components to be reported, divided into three categories: material characterization, biological characterization and details of experimental protocols. Our intention is for these proposed standards to improve reproducibility, increase quantitative comparisons of bio-nano materials, and facilitate meta analyses and in silico modelling.
430 citations
TL;DR: The objective is to provide the diverse range of researchers active in the field with an easily accessible guide to the key opportunities and challenges currently facing the nanomaterial‐mediated treatment of neurological diseases.
Abstract: Therapies directed toward the central nervous system remain difficult to translate into improved clinical outcomes. This is largely due to the blood-brain barrier (BBB), arguably the most tightly regulated interface in the human body, which routinely excludes most therapeutics. Advances in the engineering of nanomaterials and their application in biomedicine (i.e., nanomedicine) are enabling new strategies that have the potential to help improve our understanding and treatment of neurological diseases. Herein, the various mechanisms by which therapeutics can be delivered to the brain are examined and key challenges facing translation of this research from benchtop to bedside are highlighted. Following a contextual overview of the BBB anatomy and physiology in both healthy and diseased states, relevant therapeutic strategies for bypassing and crossing the BBB are discussed. The focus here is especially on nanomaterial-based drug delivery systems and the potential of these to overcome the biological challenges imposed by the BBB. Finally, disease-targeting strategies and clearance mechanisms are explored. The objective is to provide the diverse range of researchers active in the field (e.g., material scientists, chemists, engineers, neuroscientists, and clinicians) with an easily accessible guide to the key opportunities and challenges currently facing the nanomaterial-mediated treatment of neurological diseases.
340 citations
TL;DR: Recent advances are reviewed in order to better understand the impact of the biological effects of the nanoparticle–corona on nanomedicine applications.
Abstract: Engineering nanomaterials are increasingly considered promising and powerful biomedical tools or devices for imaging, drug delivery, and cancer therapies, but few nanomaterials have been tested in clinical trials. This wide gap between bench discoveries and clinical application is mainly due to the limited understanding of the biological identity of nanomaterials. When they are exposed to the human body, nanoparticles inevitably interact with bodily fluids and thereby adsorb hundreds of biomolecules. A "biomolecular corona" forms on the surface of nanomaterials and confers a new biological identity for NPs, which determines the following biological events: cellular uptake, immune response, biodistribution, clearance, and toxicity. A deep and thorough understanding of the biological effects triggered by the protein corona in vivo will speed up their translation to the clinic. To date, nearly all studies have attempted to characterize the components of protein coronas depending on different physiochemical properties of NPs. Herein, recent advances are reviewed in order to better understand the impact of the biological effects of the nanoparticle-corona on nanomedicine applications. The recent development of the impact of protein corona formation on the pharmacokinetics of nanomedicines is also highlighted. Finally, the challenges and opportunities of nanomedicine toward future clinical applications are discussed.
312 citations
TL;DR: How cancer is commonly treated in the clinic and how this relates tonanomedicine is revisited; the ongoing debate on the relevance of the EPR effect and tumor targeting is examined; ways to improve the next-generation of nanomedicines are highlighted; and the emerging concept of working with (and not against) biology is discussed.
Abstract: The interface of bio-nano science and cancer medicine is an area experiencing much progress but also beset with controversy. Core concepts of the field-e.g., the enhanced permeability and retention (EPR) effect, tumor targeting and accumulation, and even the purpose of "nano" in cancer medicine-are hotly debated. In parallel, considerable advances in neighboring fields are occurring rapidly, including the recent progress of "immuno-oncology" and the fundamental impact it is having on our understanding and the clinical treatment of the group of diseases collectively known as cancer. Herein, we (i) revisit how cancer is commonly treated in the clinic and how this relates to nanomedicine; (ii) examine the ongoing debate on the relevance of the EPR effect and tumor targeting; (iii) highlight ways to improve the next-generation of nanomedicines; and (iv) discuss the emerging concept of working with (and not against) biology. While discussing these controversies, challenges, emerging concepts, and opportunities, we explore new directions for the field of cancer nanomedicine.
282 citations
TL;DR: A detailed study of in vivo protein corona formation after blood circulation of anisotropic gold nanoparticles (nanorods and nanostars), intravenously administered in CD-1 mice and subsequently recovered is presented.
Abstract: The efficacy of drug delivery and other nanomedicine-related therapies largely relies on the ability of nanoparticles to reach the target organ. However, when nanoparticles are injected into the bloodstream, their surface is instantly modified upon interaction with blood components, principally with proteins. It is well known that a dynamic and multi-layered protein structure is formed spontaneously on the nanoparticle upon contact with physiological media, which has been termed protein corona. Although several determinant factors involved in protein corona formation have been identified from in vitro studies, specific relationships between the nanomaterial synthetic identity and its ensuing biological identity under realistic in vivo conditions remain elusive. We present here a detailed study of in vivo protein corona formation after blood circulation of anisotropic gold nanoparticles (nanorods and nanostars). Plasmonic gold nanoparticles of different shapes and sizes were coated with polyethyleneglycol, intravenously administered in CD-1 mice and subsequently recovered. The results from gel electrophoresis and mass spectrometry analysis revealed the formation of complex protein coronas, as early as 10 minutes post-injection. The total amount of protein adsorbed onto the particle surface and the protein corona composition were found to be affected by both the particle size and shape.
261 citations
References
More filters
TL;DR: The rates of protein association and dissociation are determined using surface plasmon resonance technology with nanoparticles that are thiol-linked to gold, and through size exclusion chromatography of protein–nanoparticle mixtures, and this method is developed into a systematic methodology to isolate nanoparticle-associated proteins.
Abstract: Due to their small size, nanoparticles have distinct properties compared with the bulk form of the same materials. These properties are rapidly revolutionizing many areas of medicine and technology. Despite the remarkable speed of development of nanoscience, relatively little is known about the interaction of nanoscale objects with living systems. In a biological fluid, proteins associate with nanoparticles, and the amount and presentation of the proteins on the surface of the particles leads to an in vivo response. Proteins compete for the nanoparticle "surface," leading to a protein "corona" that largely defines the biological identity of the particle. Thus, knowledge of rates, affinities, and stoichiometries of protein association with, and dissociation from, nanoparticles is important for understanding the nature of the particle surface seen by the functional machinery of cells. Here we develop approaches to study these parameters and apply them to plasma and simple model systems, albumin and fibrinogen. A series of copolymer nanoparticles are used with variation of size and composition (hydrophobicity). We show that isothermal titration calorimetry is suitable for studying the affinity and stoichiometry of protein binding to nanoparticles. We determine the rates of protein association and dissociation using surface plasmon resonance technology with nanoparticles that are thiol-linked to gold, and through size exclusion chromatography of protein-nanoparticle mixtures. This method is less perturbing than centrifugation, and is developed into a systematic methodology to isolate nanoparticle-associated proteins. The kinetic and equilibrium binding properties depend on protein identity as well as particle surface characteristics and size.
2,715 citations
TL;DR: The long-lived (“hard”) protein corona formed from human plasma is studied for a range of nanoparticles that differ in surface properties and size and both size and surface properties were found to play a very significant role.
Abstract: Nanoparticles in a biological fluid (plasma, or otherwise) associate with a range of biopolymers, especially proteins, organized into the "protein corona" that is associated with the nanoparticle and continuously exchanging with the proteins in the environment. Methodologies to determine the corona and to understand its dependence on nanomaterial properties are likely to become important in bionanoscience. Here, we study the long-lived ("hard") protein corona formed from human plasma for a range of nanoparticles that differ in surface properties and size. Six different polystyrene nanoparticles were studied: three different surface chemistries (plain PS, carboxyl-modified, and amine-modified) and two sizes of each (50 and 100 nm), enabling us to perform systematic studies of the effect of surface properties and size on the detailed protein coronas. Proteins in the corona that are conserved and unique across the nanoparticle types were identified and classified according to the protein functional properties. Remarkably, both size and surface properties were found to play a very significant role in determining the nanoparticle coronas on the different particles of identical materials. We comment on the future need for scientific understanding, characterization, and possibly some additional emphasis on standards for the surfaces of nanoparticles.
2,681 citations
TL;DR: It is shown that label-free snapshot proteomics can be used to obtain quantitative time-resolved profiles of human plasma coronas formed on silica and polystyrene nanoparticles of various size and surface functionalization.
Abstract: In biological fluids, proteins bind to the surface of nanoparticles to form a coating known as the protein corona, which can critically affect the interaction of the nanoparticles with living systems. As physiological systems are highly dynamic, it is important to obtain a time-resolved knowledge of protein-corona formation, development and biological relevancy. Here we show that label-free snapshot proteomics can be used to obtain quantitative time-resolved profiles of human plasma coronas formed on silica and polystyrene nanoparticles of various size and surface functionalization. Complex time- and nanoparticle-specific coronas, which comprise almost 300 different proteins, were found to form rapidly (<0.5 minutes) and, over time, to change significantly in terms of the amount of bound protein, but not in composition. Rapid corona formation is found to affect haemolysis, thrombocyte activation, nanoparticle uptake and endothelial cell death at an early exposure time.
1,799 citations
TL;DR: It is shown that when nanoparticles are placed in a complex biological environment, interaction with other proteins in the medium and the formation of a protein corona can 'screen' the targeting molecules on the surface of nanoparticles and cause loss of specificity in targeting.
Abstract: Nanoparticles have been proposed as carriers for drugs, genes and therapies to treat various diseases. Many strategies have been developed to target nanomaterials to specific or over-expressed receptors in diseased cells, and these typically involve functionalizing the surface of nanoparticles with proteins, antibodies or other biomolecules. Here, we show that the targeting ability of such functionalized nanoparticles may disappear when they are placed in a biological environment. Using transferrin-conjugated nanoparticles, we found that proteins in the media can shield transferrin from binding to both its targeted receptors on cells and soluble transferrin receptors. Although nanoparticles continue to enter cells, the targeting specificity of transferrin is lost. Our results suggest that when nanoparticles are placed in a complex biological environment, interaction with other proteins in the medium and the formation of a protein corona can 'screen' the targeting molecules on the surface of nanoparticles and cause loss of specificity in targeting.
1,484 citations
TL;DR: A carbamate derivative of PEG-1900 with distearoylphosphatidylethanolamine (PEG-DSPE) had the greatest ability to decrease MPS uptake of liposomes, at optimum concentrations of 5-7 mol% in liposome composed of sphingomyelin/egg phosphatidylcholine/cholesterol (SM/PC/Chol, 1:1:1, molar ratio).
1,375 citations