Abstract:Proteins bound to nanoparticle surfaces are known to affect particle clearance by influencing immune cell uptake and distribution to the organs of the mononuclear phagocytic system. The composition of the protein corona has been described for several types of nanomaterials, but the role of the corona in nanoparticle biocompatibility is not well established. In this study we investigate the role of nanoparticle surface properties (PEGylation) and incubation times on the protein coronas of colloidal gold nanopar… Show more
“…It is quite challenging to precisely characterize the composition of a protein corona because of its complex and dynamic nature [49]. However simple SDS-PAGE gel electrophoresis of desorbed proteins from NP previously incubated in a culture medium supplemented with serum can give some interesting insights.…”
functionalization is often used to improve NP biocompatibility or to enhance cellular uptake. But in biological media, the formation of a protein corona adds a level of complexity. The aim of this study was to investigate in vitro the influence of NP surface functionalization on their cellular uptake and the biological response induced. 50nm fluorescent silica NP were functionalized either with amine or carboxylic groups, in presence or in absence of polyethylene glycol (PEG). NP were incubated with macrophages, cellular uptake and cellular response were assessed in terms of cytotoxicity, pro-inflammatory response and oxidative stress. The NP protein corona was also characterized by protein mass spectroscopy. Results showed that NP uptake was enhanced in absence of PEG, while NP adsorption at the cell membrane was fostered by an initial positively charged NP surface. NP toxicity was not correlated with NP uptake. NP surface functionalization also influenced the formation of the protein corona as the profile of protein binding differed among the NP types.
“…It is quite challenging to precisely characterize the composition of a protein corona because of its complex and dynamic nature [49]. However simple SDS-PAGE gel electrophoresis of desorbed proteins from NP previously incubated in a culture medium supplemented with serum can give some interesting insights.…”
functionalization is often used to improve NP biocompatibility or to enhance cellular uptake. But in biological media, the formation of a protein corona adds a level of complexity. The aim of this study was to investigate in vitro the influence of NP surface functionalization on their cellular uptake and the biological response induced. 50nm fluorescent silica NP were functionalized either with amine or carboxylic groups, in presence or in absence of polyethylene glycol (PEG). NP were incubated with macrophages, cellular uptake and cellular response were assessed in terms of cytotoxicity, pro-inflammatory response and oxidative stress. The NP protein corona was also characterized by protein mass spectroscopy. Results showed that NP uptake was enhanced in absence of PEG, while NP adsorption at the cell membrane was fostered by an initial positively charged NP surface. NP toxicity was not correlated with NP uptake. NP surface functionalization also influenced the formation of the protein corona as the profile of protein binding differed among the NP types.
“…This procedure creates a hydrodynamic radius around the surface of NPs, which is efficient in reducing the overall amount of serum adsorbed proteins, thus reducing macrophagedriven clearance, but does not affect their qualitative composition [148,149]. Furthermore, PEG plays a critical role in triggering inflammatory and immunogenic phenomena [51].…”
In a perfect sequence of events, nanoparticles (NPs) are injected into the bloodstream where they circulate until they reach the target tissue. The ligand on the NP surface recognizes its specific receptor expressed on the target tissue and the drug is released in a controlled manner. However, once injected in a physiological environment, NPs interact with biological components and are surrounded by a protein corona (PC). This can trigger an immune response and affect NP toxicity and targeting capabilities. In this review, we provide a survey of recent findings on the NP–PC interactions and discuss how the PC can be used to modulate both cytotoxicity and the immune response as well as to improve the efficacy of targeted delivery of nanocarriers.
“…[57][58][59] Although often referred to as protein corona, also other molecules, such as lipids, can adhere to the NMs. 57,60 The effect of the corona on the distribution and biocompatibility of NMs is not well understood yet.…”
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confidence: 99%
“…Coating with polyethylene glycol (PEG) has been shown to enable escape from the MPS for a prolonged period of time, thereby increasing the half-life in blood. 86,87 Dobrovolskaia et al 60 reported recently that the molecular weight of PEG coating affected the total amount of protein binding. However, the types of proteins forming the protein corona were not influenced by …”
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confidence: 99%
“…60 While increasing half-life in blood may be an advantage for the therapeutic or diagnostic efficacy of NMPs, it is important to realize that a modulation of the kinetics and distribution of NMPs by applying various types and amounts of PEG coating may also modify its toxicity profile. 18,35,63 Therefore, a balance of hydrophilic and hydrophobic coating is needed for an optimal circulation of NMPs in the system.…”
Nanomaterials (NMs) are attractive for biomedical and pharmaceutical applications because of their unique physicochemical and biological properties. A major application area of NMs is drug delivery. Many nanomedicinal products (NMPs) currently on the market or in clinical trials are most often based on liposomal products or polymer conjugates. NMPs can be designed to target specific tissues, eg, tumors. In virtually all cases, NMPs will eventually reach the immune system. It has been shown that most NMs end up in organs of the mononuclear phagocytic system, notably liver and spleen. Adverse immune effects, including allergy, hypersensitivity, and immunosuppression, have been reported after NMP administration. Interactions of NMPs with the immune system may therefore constitute important side effects. Currently, no regulatory documents are specifically dedicated to evaluate the immunotoxicity of NMs or NMPs. Their immunotoxicity assessment is performed based on existing guidelines for conventional substances or medicinal products. Due to the unique properties of NMPs when compared with conventional medicinal products, it is uncertain whether the currently prescribed set of tests provides sufficient information for an adequate evaluation of potential immunotoxicity of NMPs. The aim of this study was therefore, to compare the current regulatory immunotoxicity testing requirements with the accumulating knowledge on immunotoxic effects of NMPs in order to identify potential gaps in the safety assessment. This comparison showed that immunotoxic effects, such as complement activation-related pseudoallergy, myelosuppression, inflammasome activation, and hypersensitivity, are not readily detected by using current testing guidelines. Immunotoxicity of NMPs would be more accurately evaluated by an expanded testing strategy that is equipped to stratify applicable testing for the various types of NMPs.
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