Anti-polyethylene glycol antibodies alter the protein corona deposited on nanoparticles and the physiological pathways regulating their fate in vivo

Grenier, Pierre; Viana, Iara Maíra de Oliveira; Lima, Eliana Martins; Bertrand, Nicolas

doi:10.1016/j.jconrel.2018.08.022

Cited by 103 publications

(78 citation statements)

References 53 publications

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“…However, the mechanism of clearance dependent on the presence of anti-PEG antibody is only partially understood. A recent study by Grenier et al (2018) focused on the clearance rate of different PEGylated molecules, such as PLGA NPs, liposomes, and BSA, which demonstrated how even a single administration of PEG-PLGA NPs could induce the production of anti-PEG IgM and increase NP clearance by their activation of the complement system through the classical pathway. This not only reduced the circulation time of PEG-PLGA NPs after a second administration but also induced cross-reaction toward PEGylated liposomes, increasing also their clearance.…”

Section: Synthetic Approachesmentioning

confidence: 99%

Recent Advances in Understanding the Protein Corona of Nanoparticles and in the Formulation of “Stealthy” Nanomaterials

Rampado

Crotti

Caliceti

et al. 2020

Front. Bioeng. Biotechnol.

245

166

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In the last decades, the staggering progress in nanotechnology brought around a wide and heterogeneous range of nanoparticle-based platforms for the diagnosis and treatment of many diseases. Most of these systems are designed to be administered intravenously. This administration route allows the nanoparticles (NPs) to widely distribute in the body and reach deep organs without invasive techniques. When these nanovectors encounter the biological environment of systemic circulation, a dynamic interplay occurs between the circulating proteins and the NPs, themselves. The set of proteins that bind to the NP surface is referred to as the protein corona (PC). PC has a critical role in making the particles easily recognized by the innate immune system, causing their quick clearance by phagocytic cells located in organs such as the lungs, liver, and spleen. For the same reason, PC defines the immunogenicity of NPs by priming the immune response to them and, ultimately, their immunological toxicity. Furthermore, the protein corona can cause the physical destabilization and agglomeration of particles. These problems induced to consider the PC only as a biological barrier to overcome in order to achieve efficient NP-based targeting. This review will discuss the latest advances in the characterization of PC, development of stealthy NP formulations, as well as the manipulation and employment of PC as an alternative resource for prolonging NP half-life, as well as its use in diagnostic applications.

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Section: Synthetic Approachesmentioning

confidence: 99%

Recent Advances in Understanding the Protein Corona of Nanoparticles and in the Formulation of “Stealthy” Nanomaterials

Rampado

Crotti

Caliceti

et al. 2020

Front. Bioeng. Biotechnol.

245

166

View full text Add to dashboard Cite

show abstract

“…Engineered nanoparticles (NPs) for biomedical applications undergo spontaneous protein adhesion when placed in biological fluids, such as blood. This phenomenon is known as protein corona [ 1 ] and it has direct implications in the cellular uptake, [ 2 ] circulating times, [ 3 ] fate, [ 4 ] and toxicity [ 5 ] of NPs in living beings. Thus, in order to learn about the NPs' interaction with proteins and cells, in situ characterization would be helpful, that is, quantification methods without the need to isolate NPs from their environment.…”

Section: Introductionmentioning

confidence: 99%

Toward Diffusion Measurements of Colloidal Nanoparticles in Biological Environments by Nuclear Magnetic Resonance

Padró

Cienskowski

López-Fernández

et al. 2020

Small

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Protein corona formation on the surface of nanoparticles (NPs) is observed in situ by measuring diffusion coefficients of the NPs under the presence of proteins with a 19F nuclear magnetic resonance (NMR) based methodology. Formation of a protein corona reduces the diffusion coefficient of the NPs, based on an increase in their effective hydrodynamic radii. With this methodology it is demonstrated that the apparent dissociation constant of protein–NP complexes may vary over at least nine orders of magnitude for different types of proteins, in line with the Vroman effect. Using this methodology, the interaction between one type of protein and one type of nanoparticle can be studied quantitatively. Due to the NMR‐based detection, this methodology has no interference by absorption/scattering effects, by which optical detection schemes are affected. By using the potential of the NMR chemical shift, the detection of multiple 19F signals simultaneously opens the possibility to study the diffusion of several NPs at the same time. The 19F labeling of the NPs has negligible effect on their acute toxicity and moderate effect on NPs uptake by cells.

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“…Pre-existing anti-PEG antibodies have also been linked to allergic reactions after the infusion of pegylated medicines [29,31]. However, other studies have reported that anti-PEG IgM cannot accelerate the clearance of pegylated proteins [37]. Taken together, there is a need to investigate the effects of anti-PEG antibodies on pegylated drugs.…”

Section: Introductionmentioning

confidence: 99%

Both IgM and IgG Antibodies against Polyethylene Glycol Can Alter the Biological Activity of Methoxy Polyethylene Glycol-Epoetin Beta in Mice

et al. 2019

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Pre-existing antibodies that bind polyethylene glycol are present in about 40% of healthy individuals. It is currently unknown if pre-existing anti-polyethylene glycol (PEG) antibodies can alter the bioactivity of pegylated drugs with a single long PEG chain, which represents the majority of newly developed pegylated medicines. Methoxy polyethylene glycol-epoetin beta (PEG-EPO) contains a single 30 kDa PEG chain and is used to treat patients suffering from anemia. We find that the pre-existing human anti-PEG IgM and IgG antibodies from normal donors can bind to PEG-EPO. The prevalence and concentrations of anti-PEG IgM and IgG antibodies were also higher in patients that responded poorly to PEG-EPO. Monoclonal anti-PEG IgM and IgG antibodies at concentrations found in normal donors blocked the biological activity of PEG-EPO to stimulate the production of new erythrocytes in mice and accelerated the clearance of 125 I-PEG-EPO, resulting in PEG-EPO accumulation primarily in the liver and spleen. Accelerated clearance by the anti-PEG IgG antibody was mediated by the Fc portion of the antibody. Importantly, infusing higher doses of PEG-EPO could compensate for the inhibitory effects of anti-PEG antibodies, suggesting that pre-existing anti-PEG antibodies can be "dosed through." Our study indicates that the bioactivity and therapeutic activity of PEG-EPO may be reduced in patients with elevated levels of pre-existing anti-PEG antibodies. New pegylated medicines with a single long PEG chain may also be affected in patients with high levels of anti-PEG antibodies.

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Anti-polyethylene glycol antibodies alter the protein corona deposited on nanoparticles and the physiological pathways regulating their fate in vivo

Cited by 103 publications

References 53 publications

Recent Advances in Understanding the Protein Corona of Nanoparticles and in the Formulation of “Stealthy” Nanomaterials

Recent Advances in Understanding the Protein Corona of Nanoparticles and in the Formulation of “Stealthy” Nanomaterials

Toward Diffusion Measurements of Colloidal Nanoparticles in Biological Environments by Nuclear Magnetic Resonance

Both IgM and IgG Antibodies against Polyethylene Glycol Can Alter the Biological Activity of Methoxy Polyethylene Glycol-Epoetin Beta in Mice

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