scholarly journals The fate of a designed protein corona on nanoparticles in vitro and in vivo

2015 ◽  
Vol 6 ◽  
pp. 36-46 ◽  
Author(s):  
Denise Bargheer ◽  
Julius Nielsen ◽  
Gabriella Gébel ◽  
Markus Heine ◽  
Sunhild C Salmen ◽  
...  
Keyword(s):  
Superparamagnetic Iron Oxide ◽  
Protein Corona ◽  
Blood Stream ◽  
Minor Importance ◽  
Iron Oxide Particles ◽  
Corona Formation ◽  
The Stability ◽  
Covalently Bound

A variety of monodisperse superparamagnetic iron oxide particles (SPIOs) was designed in which the surface was modified by PEGylation with mono- or bifunctional poly(ethylene oxide)amines (PEG). Using 125I-labeled test proteins (transferrin, albumin), the binding and exchange of corona proteins was studied first in vitro. Incubation with 125I-transferrin showed that with increasing grade of PEGylation the binding was substantially diminished without a difference between simply adsorbed and covalently bound protein. However, after incubation with excess albumin and subsequently whole plasma, transferrin from the preformed transferrin corona was more and more lost from SPIOs in the case of adsorbed proteins. If non-labeled transferrin was used as preformed corona and excess 125I-labeled albumin was added to the reaction mixtures with different SPIOs, a substantial amount of label was bound to the particles with initially adsorbed transferrin but little or even zero with covalently bound transferrin. These in vitro experiments show a clear difference in the stability of a preformed hard corona with adsorbed or covalently bound protein. This difference seems, however, to be of minor importance in vivo when polymer-coated 59Fe-SPIOs with adsorbed or covalently bound 125I-labeled mouse transferrin were injected intravenously in mice. With both protein coronae the 59Fe/125I-labelled particles were cleared from the blood stream within 30 min and appeared in the liver and spleen to a large extent (>90%). In addition, after 2 h already half of the 125I-labeled transferrin from both nanodevices was recycled back into the plasma and into tissue. This study confirms that adsorbed transferrin from a preformed protein corona is efficiently taken up by cells. It is also highlighted that a radiolabelling technique described in this study may be of value to investigate the role of protein corona formation in vivo for the respective nanoparticle uptake.

scholarly journals Biological Characteristics of Fluorescent Superparamagnetic Iron Oxide Labeled Human Dental Pulp Stem Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Liang Ma ◽  
Ming-wei Li ◽  
Yu Bai ◽  
Hui-hui Guo ◽  
Sheng-chao Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Iron Oxide ◽  
Dental Pulp ◽  
Superparamagnetic Iron Oxide ◽  
Biological Properties ◽  
Dental Pulp Stem Cells ◽  
Iron Oxide Particles ◽  
Human Dental Pulp

Tracking transplanted stem cells is necessary to clarify cellular properties and improve transplantation success. In this study, we investigate the effects of fluorescent superparamagnetic iron oxide particles (SPIO) (Molday ION Rhodamine-B™, MIRB) on biological properties of human dental pulp stem cells (hDPSCs) and monitor hDPSCs in vitro and in vivo using magnetic resonance imaging (MRI). Morphological analysis showed that intracellular MIRB particles were distributed in the cytoplasm surrounding the nuclei of hDPSCs. 12.5–100 μg/mL MIRB all resulted in 100% labeling efficiency. MTT showed that 12.5–50 μg/mL MIRB could promote cell proliferation and MIRB over 100 μg/mL exhibited toxic effect on hDPSCs. In vitro MRI showed that 1 × 106cells labeled with various concentrations of MIRB (12.5–100 μg/mL) could be visualized. In vivo MRI showed that transplanted cells could be clearly visualized up to 60 days after transplantation. These results suggest that 12.5–50 μg/mL MIRB is a safe range for labeling hDPSCs. MIRB labeled hDPSCs cell can be visualized by MRI in vitro and in vivo. These data demonstrate that MIRB is a promising candidate for hDPSCs tracking in hDPSCs based dental pulp regeneration therapy.

scholarly journals In vivo Protein Corona Formation: Characterizations, Effects on Engineered Nanoparticles’ Biobehaviors, and Applications

2021 ◽  
Vol 9 ◽  
Author(s):  
Xue Bai ◽  
Jiali Wang ◽  
Qingxin Mu ◽  
Gaoxing Su
Keyword(s):  
Blood Circulation ◽  
Biological Systems ◽  
Protein Corona ◽  
Engineered Nanoparticles ◽  
Physiochemical Properties ◽  
Characterization Methods ◽  
The Past ◽  
Corona Formation

Understanding the basic interactions between engineered nanoparticles (ENPs) and biological systems is essential for evaluating ENPs’ safety and developing better nanomedicine. Profound interactions between ENPs and biomolecules such as proteins are inevitable to occur when ENPs are administered or exposed to biological systems, for example, through intravenous injection, oral, or respiration. As a key component of these interactions, protein corona (PC) is immediately formed surrounding the outlayer of ENPs. PC formation is crucial because it gives ENPs a new biological identity by altering not only the physiochemical properties, but also the biobehaviors of ENPs. In the past two decades, most investigations about PC formation were carried out with in vitro systems which could not represent the true events occurring within in vivo systems. Most recently, studies of in vivo PC formation were reported, and it was found that the protein compositions and structures were very different from those formed in vitro. Herein, we provide an in-time review of the recent investigations of this in vivo PC formation of ENPs. In this review, commonly used characterization methods and compositions of in vivo PC are summarized firstly. Next, we highlight the impacts of the in vivo PC formation on absorption, blood circulation, biodistribution, metabolism, and toxicity of administered ENPs. We also introduce the applications of modulating in vivo PC formation in nanomedicine. We further discuss the challenges and future perspectives.

scholarly journals Understanding the Influence of a Bifunctional Polyethylene Glycol Derivative in Protein Corona Formation around Iron Oxide Nanoparticles

Materials ◽  
2019 ◽  
Vol 12 (14) ◽  
pp. 2218 ◽  
Author(s):  
Amalia Ruiz ◽  
Adán Alpízar ◽  
Lilianne Beola ◽  
Carmen Rubio ◽  
Helena Gavilán ◽  
...  
Keyword(s):  
Polyethylene Glycol ◽  
Iron Oxide ◽  
Iron Oxide Nanoparticles ◽  
Protein Corona ◽  
Raw 264.7 Cells ◽  
Oxide Nanoparticles ◽  
Mri Imaging ◽  
Corona Formation

Superparamagnetic iron oxide nanoparticles are one of the most prominent agents used in theranostic applications, with MRI imaging the main application assessed. The biomolecular interface formed on the surface of a nanoparticle in a biological medium determines its behaviour in vitro and in vivo. In this study, we have compared the formation of the protein corona on highly monodisperse iron oxide nanoparticles with two different coatings, dimercaptosuccinic acid (DMSA), and after conjugation, with a bifunctional polyethylene glycol (PEG)-derived molecule (2000 Da) in the presence of Wistar rat plasma. The protein fingerprints around the nanoparticles were analysed in an extensive proteomic study. The results presented in this work indicate that the composition of the protein corona is very difficult to predict. Proteins from different functional categories—cell components, lipoproteins, complement, coagulation, immunoglobulins, enzymes and transport proteins—were identified in all samples with very small variability. Although both types of nanoparticles have similar amounts of bonded proteins, very slight differences in the composition of the corona might explain the variation observed in the uptake and biotransformation of these nanoparticles in Caco-2 and RAW 264.7 cells. Cytotoxicity was also studied using a standard 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. Controlling nanoparticles’ reactivity to the biological environment by deciding on its surface functionalization may suggest new routes in the control of the biodistribution, biodegradation and clearance of multifunctional nanomedicines.

scholarly journals Human inhalation exposure to iron oxide particles

2013 ◽  
Vol 14 (1-2) ◽  
pp. 5-23 ◽  
Author(s):  
Nastassja Lewinski ◽  
Halshka Graczyk ◽  
Michael Riediker
Keyword(s):  
Iron Oxide ◽  
Iron Oxide Nanoparticles ◽  
Clinical Studies ◽  
Superparamagnetic Iron Oxide ◽  
Oxide Nanoparticles ◽  
Inhalation Toxicity ◽  
Iron Oxide Particles ◽  
Oxide Particles

AbstractIn the past decade, many studies have been conducted to determine the health effects induced by exposure to engineered nanomaterials (NMs). Specifically for exposure via inhalation, numerous in vitro and animal in vivo inhalation toxicity studies on several types of NMs have been published. However, these results are not easily extrapolated to judge the effects of inhaling NMs in humans, and few published studies on the human response to inhalation of NMs exist. Given the emergence of more industries utilizing iron oxide nanoparticles as well as more nanomedicine applications of superparamagnetic iron oxide nanoparticles (SPIONs), this review presents an overview of the inhalation studies that have been conducted in humans on iron oxides. Both occupational exposure studies on complex iron oxide dusts and fumes, as well as human clinical studies on aerosolized, micron-size iron oxide particles are discussed. Iron oxide particles have not been described to elicit acute inhalation response nor promote lung disease after chronic exposure. The few human clinical studies comparing inhalation of fine and ultrafine metal oxide particles report no acute changes in the health parameters measured. Taken together existing evidence suggests that controlled human exposure to iron oxide nanoparticles, such as SPIONs, could be conducted safely.

scholarly journals Internalisation and Biological Activity of Nucleic Acids Delivering Cell-Penetrating Peptide Nanoparticles Is Controlled by the Biomolecular Corona

2021 ◽  
Vol 14 (7) ◽  
pp. 667
Author(s):  
Annely Lorents ◽  
Maria Maloverjan ◽  
Kärt Padari ◽  
Margus Pooga
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Transfection Efficiency ◽  
Protein Corona ◽  
Blood Stream ◽  
Cell Penetrating Peptides ◽  
Biological Efficiency ◽  
Cell Penetrating

Nucleic acid molecules can be transferred into cells to alter gene expression and, thus, alleviate certain pathological conditions. Cell-penetrating peptides (CPPs) are vectors that can be used for transfecting nucleic acids as well as many other compounds. CPPs associate nucleic acids non-covalently, forming stable nanoparticles and providing efficient transfection of cells in vitro. However, in vivo, expected efficiency is achieved only in rare cases. One of the reasons for this discrepancy is the formation of protein corona around nanoparticles, once they are exposed to a biological environment, e.g., blood stream. In this study, we compared protein corona of CPP-nucleic acid nanoparticles formed in the presence of bovine, murine and human serum. We used Western blot and mass-spectrometry to identify the major constituents of protein corona forming around nanoparticles, showing that proteins involved in transport, haemostasis and complement system are its major components. We investigated physical features of nanoparticles and measured their biological efficiency in splice-correction assay. We showed that protein corona constituents might alter the fate of nanoparticles in vivo, e.g., by subjecting them to phagocytosis. We demonstrated that composition of protein corona of nanoparticles is species-specific that leads to dissimilar transfection efficiency and should be considered while developing delivery systems for nucleic acids.

scholarly journals Internalisation and biological activity of nucleic acids delivering cell-penetrating peptide nanoparticles is controlled by the biomolecular corona

2021 ◽  
Author(s):  
Annely Lorents ◽  
Maria Maloverjan ◽  
Kärt Padari ◽  
Margus Pooga
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Transfection Efficiency ◽  
Protein Corona ◽  
Blood Stream ◽  
Cell Penetrating Peptides ◽  
Biological Efficiency ◽  
Cell Penetrating

Nucleic acid molecules can be transferred into cells to alter gene expression and, thus, alleviate certain pathological conditions. Cell-penetrating peptides (CPPs) are vectors that can be used for transfecting nucleic acids as well as many other compounds. CPPs associate nucleic acids non-covalently, forming stable nanoparticles and providing efficient transfection of cells in vitro. However, in vivo, expected efficiency is achieved only in rare cases. One of the reasons for this discrepancy is formation of protein corona around nanoparticles, once they are exposed to a biological environment, e.g. blood stream. In this study, we compared CPP-nucleic acid nanoparticles formed in the presence of bovine, murine and human serum. We used Western blot and mass-spectrometry to identify the major constituents of protein corona forming around nanoparticles, showing that proteins involved in transport, haemostasis and complement system are its major components. We investigated physical features of nanoparticles, and measured their biological efficiency in splice-correction assay. We showed that protein corona constituents might alter the fate of nanoparticles in vivo, e.g. by subjecting them to phagocytosis. We demonstrated that composition of protein corona of nanoparticles is species-specific that leads to dissimilar transfection efficiency and should be taken into account while developing delivery systems for nucleic acids.

scholarly journals Efficient In Vitro Labeling of Human Neural Precursor Cells with Superparamagnetic Iron Oxide Particles: Relevance for In Vivo Cell Tracking

Stem Cells ◽  
2008 ◽  
Vol 26 (2) ◽  
pp. 505-516 ◽  
Author(s):  
Margherita Neri ◽  
Claudio Maderna ◽  
Chiara Cavazzin ◽  
Vivien Deidda-Vigoriti ◽  
Letterio S. Politi ◽  
...  
Keyword(s):  
Iron Oxide ◽  
Cell Tracking ◽  
Superparamagnetic Iron Oxide ◽  
Neural Precursor Cells ◽  
Neural Precursor ◽  
Iron Oxide Particles ◽  
Superparamagnetic Iron Oxide Particles ◽  
Oxide Particles

Formation and Structure of Casein Micelles in Lactating Mammary Tissue

1970 ◽  
Vol 28 ◽  
pp. 150-151
Author(s):  
Robert J. Carroll ◽  
Marvin P. Thompson ◽  
Harold M. Farrell
Keyword(s):  
Size Distribution ◽  
G Protein ◽  
Milk Proteins ◽  
Mammary Tissue ◽  
Colloidal System ◽  
Casein Micelles ◽  
The Stability

Milk is an unusually stable colloidal system; the stability of this system is due primarily to the formation of micelles by the major milk proteins, the caseins. Numerous models for the structure of casein micelles have been proposed; these models have been formulated on the basis of in vitro studies. Synthetic casein micelles (i.e., those formed by mixing the purified αsl- and k-caseins with Ca2+ in appropriate ratios) are dissimilar to those from freshly-drawn milks in (i) size distribution, (ii) ratio of Ca/P, and (iii) solvation (g. water/g. protein). Evidently, in vivo organization of the caseins into the micellar form occurs in-a manner which is not identical to the in vitro mode of formation.

Kinetics of Various 99mTc-Sn-Pyrophosphate Compounds in the Rat

1977 ◽  
Vol 16 (04) ◽  
pp. 157-162 ◽  
Author(s):  
C. Schümichen ◽  
B. Mackenbrock ◽  
G. Hoffmann
Keyword(s):  
Normal Saline ◽  
Half Life ◽  
Compound A ◽  
Short Half Life ◽  
Low Concentrations ◽  
The Stability ◽  
Kinetics Of ◽  
In Vitro Stability

SummaryThe bone-seeking 99mTc-Sn-pyrophosphate compound (compound A) was diluted both in vitro and in vivo and proved to be unstable both in vitro and in vivo. However, stability was much better in vivo than in vitro and thus the in vitro stability of compound A after dilution in various mediums could be followed up by a consecutive evaluation of the in vivo distribution in the rat. After dilution in neutral normal saline compound A is metastable and after a short half-life it is transformed into the other 99mTc-Sn-pyrophosphate compound A is metastable and after a short half-life in bone but in the kidneys. After dilution in normal saline of low pH and in buffering solutions the stability of compound A is increased. In human plasma compound A is relatively stable but not in plasma water. When compound B is formed in a buffering solution, uptake in the kidneys and excretion in urine is lowered and blood concentration increased.It is assumed that the association of protons to compound A will increase its stability at low concentrations while that to compound B will lead to a strong protein bond in plasma. It is concluded that compound A will not be stable in vivo because of a lack of stability in the extravascular space, and that the protein bond in plasma will be a measure of its in vivo stability.

Applicability of Instability Index for In vitro Protein Stability Prediction

2019 ◽  
Vol 26 (5) ◽  
pp. 339-347 ◽  
Author(s):  
Dilani G. Gamage ◽  
Ajith Gunaratne ◽  
Gopal R. Periyannan ◽  
Timothy G. Russell
Keyword(s):  
Protein Stability ◽  
Caulobacter Crescentus ◽  
Effect Of Temperature ◽  
Instability Index ◽  
Dipeptide Composition ◽  
Experimental Conditions ◽  
The Stability ◽  
Vitro Protein

Background: The dipeptide composition-based Instability Index (II) is one of the protein primary structure-dependent methods available for in vivo protein stability predictions. As per this method, proteins with II value below 40 are stable proteins. Intracellular protein stability principles guided the original development of the II method. However, the use of the II method for in vitro protein stability predictions raises questions about the validity of applying the II method under experimental conditions that are different from the in vivo setting. Objective: The aim of this study is to experimentally test the validity of the use of II as an in vitro protein stability predictor. Methods: A representative protein CCM (CCM - Caulobacter crescentus metalloprotein) that rapidly degrades under in vitro conditions was used to probe the dipeptide sequence-dependent degradation properties of CCM by generating CCM mutants to represent stable and unstable II values. A comparative degradation analysis was carried out under in vitro conditions using wildtype CCM, CCM mutants and two other candidate proteins: metallo-β-lactamase L1 and α -S1- casein representing stable, borderline stable/unstable, and unstable proteins as per the II predictions. The effect of temperature and a protein stabilizing agent on CCM degradation was also tested. Results: Data support the dipeptide composition-dependent protein stability/instability in wt-CCM and mutants as predicted by the II method under in vitro conditions. However, the II failed to accurately represent the stability of other tested proteins. Data indicate the influence of protein environmental factors on the autoproteolysis of proteins. Conclusion: Broader application of the II method for the prediction of protein stability under in vitro conditions is questionable as the stability of the protein may be dependent not only on the intrinsic nature of the protein but also on the conditions of the protein milieu.

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