The development of stable aqueous suspensions of PEGylated SPIONs for biomedical applications

Hervé, Katel; Douziech-Eyrolles, Laurence; Munnier, Emilie; Cohen-Jonathan, Simone; Soucé, Martin; Marchais, H.; Limelette, P.; Warmont, Fabienne; Saboungi, Marie‐Louise; Dubois, Pierre; Chourpa, Igor

doi:10.1088/0957-4484/19/46/465608

Cited by 122 publications

(118 citation statements)

References 34 publications

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“…Because polyethylene glycol (PEG) coatings stabilize MNPs in physiological fl uids and impart an additional biocompatibility to the system for applications in neuronal cultures, [ 34 ] carbodiimide chemistry was used to graft 10 kDa PEG chains onto the poly(acrylic acid) (PAA)-passivated water-soluble MNPs. In order to ensure close proximity during AMF application, MNPs must be specifi cally targeted to Aβ aggregates.…”

Section: Targeting Mnps To Aβmentioning

confidence: 99%

“…While the biocompatibility of iron oxide MNPs has been established in numerous in vitro and in vivo studies, [29][30][31][32]34 ] including our earlier work, [ 40 ] here we aimed to evaluate the potential neurotoxic effects of magnetothermal disaggregation of Aβ. Specifi cally, a number of reports indicate that soluble Aβ oligomers may yield greater neurotoxicity than larger aggregates.…”

Section: Effect Of Magnetothermal Disruption Of Aβ Aggregates On Neurmentioning

confidence: 99%

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Targeted Magnetic Nanoparticles for Remote Magnetothermal Disruption of Amyloid‐β Aggregates

Loynachan

Romero

Christiansen

et al. 2015

Adv Healthcare Materials

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Remotely triggered hysteretic heat dissipation by magnetic nanoparticles (MNPs) selectively attached to targeted proteins can be used to break up self-assembled aggregates. This magnetothermal approach is applied to the amyloid-β (Aβ) protein, which forms dense, insoluble plaques characteristic of Alzheimer's disease. Specific targeting of dilute MNPs to Aβ aggregates is confirmed via transmission electron microscopy (TEM) and is found to be consistent with a statistical model of MNP distribution on the Aβ substrates. MNP composition and size are selected to achieve efficient hysteretic power dissipation at physiologically safe alternating magnetic field (AMF) conditions. Dynamic light scattering, fluorescence spectroscopy, and TEM are used to characterize the morphology and size distribution of aggregates before and after exposure to AMF. A dramatic reduction in aggregate size from microns to tens of nanometers is observed, suggesting that exposure to an AMF effectively destabilizes Aβ deposits decorated with targeted MNPs. Experiments in primary hippocampal neuronal cultures indicate that the magnetothermal disruption of aggregates reduces Aβ cytotoxicity, which may enable future applications of this approach for studies of protein disaggregation in physiological environments.

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Section: Targeting Mnps To Aβmentioning

confidence: 99%

Section: Effect Of Magnetothermal Disruption Of Aβ Aggregates On Neurmentioning

confidence: 99%

Targeted Magnetic Nanoparticles for Remote Magnetothermal Disruption of Amyloid‐β Aggregates

Loynachan

Romero

Christiansen

et al. 2015

Adv Healthcare Materials

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“…Indeed, PEG is a well-known material in providing protein adsorption resistance [42]. This strategy is mostly used for drug delivery, while no reports are present in the literature with respect to bioassays [43,44]. Afterwards, the G6 peptide was conjugated on PEG-MP obtaining a surface conjugation density of 12.5 Â 10 12 peptide cm 22 corresponding to an average distance between each peptide of approximately 30 nm.…”

Section: Discussionmentioning

confidence: 99%

“…Several examples show how peptide can be conjugated to MP. However, none of them report about the use of antifouling surfaces such as PEG decorated with targeting peptide for diagnostic applications [43,44].…”

Section: Introductionmentioning

confidence: 99%

Integration of binding peptide selection and multifunctional particles as tool-box for capture of soluble proteins in serum

Cusano

Causa

Moglie

et al. 2014

J. R. Soc. Interface.

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In this paper, we report on a general approach for the detection of a specific tumoural biomarker directly in serum. Such detection is made possible using a protein-binding peptide selected through an improved phage display technique and then conjugated to engineered microparticles (MPs). Protein biomarkers represent an unlimited source of information for non-invasive diagnostic and prognostic tests; MP-based assays are becoming largely used in manipulation of soluble biomarkers, but their direct use in serum is hampered by the complex biomolecular environment. Our technique overcomes the current limitations as it produces a selective MP-engineered with an antifouling layer-that 'captures' the relevant protein staying impervious to the background. Our system succeeds in fishing-out the human tumour necrosis factor alpha directly in serum with a high selectivity degree. Our method could have great impact in soluble protein manipulation and detection for a wide variety of diagnostic applications.

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“…PEG is an attractive polymer for reducing opsonization due to its uncharged and hydrophilic nature Chess, 2003, Harris et al, 2001). It has been shown that the presence of PEG chains on the nanocarrier surface increases both the colloidal stability in physiological conditions (Hervé et al, 2008) and the in vivo blood half-life . The stealthiness of a PEGylated nanocarrier can also be affected by parameters such as the polymer molecular weight, as well as its density and conformation on the nanocarrier surface , Peracchia et al, 1997.…”

Section: Introductionmentioning

confidence: 99%

Tailorable nanocarrier emulsion for drug delivery

Zeng¹

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Close to 40-percent of new pharmaceuticals and over 30-percent of pipeline drugs exhibit poor water solubility which provides challenges in drug delivery, such as the delivery of therapeutic levels of drugs to specific biological targets to achieve a desired therapeutic outcome. The challenge of increasing drug therapeutic efficacy, with a concurrent minimization of side effects, can be tackled through proper design and engineering of a suitable drug delivery system (DDS). There is a high demand for DDS that are easy to prepare in the absence of non-pharmaceutical solvents, can carry a variety of drugs, have appropriate pharmacokinetic properties including stability under biological conditions and/or can deliver a drug to a particular tissue or receptor. The development of nanotechnology and bioengineered nanomaterials has greatly increased the potential of nanocarriers for drug delivery. Motivated by the challenges experienced with modular design of effective nanocarrier, this PhD project aims to develop a platform tailorable nanocarrier emulsion (TNE) with combined long circulating and target specific properties, using only biological components and facile processes.Nanoemulsions are a promising nanocarrier class for enhancement of solubility and bioavailability of poorly soluble drugs. They are emulsions that have extremely small droplet size ranging from 10 nm to 200 nm with narrow size distribution. The enormous interfacial area formed by nano-sized droplets provides further engineering opportunities for sustained and controlled drug delivery. Peptide surfactant AM1 was shown to have good emulsification properties and can stabilize oil-in-water emulsions prepared from a range of oils. Recent works from our laboratory have shown that AM1 stabilized emulsion can be used to deliver a hydrophobic molecule to knock down an intracellular protein target in vitro. In this PhD work, we tested our hypotheses that a recently-reported biosurfactant protein DAMP4, which comprises four repeating sequences closely related to AM1, could be used to functionalize the interface of AM1 stabilized oil-in-water emulsion through non-covalent self-assembly by addressing the following: (1) Utilization of DAMP4 modified with polyethylene glycol (PEG) to investigate whether DAMP4 can display PEG at the interface and impart altered cell association to the nanoemulsion; (2) Utilization of DAMP4 modified with monoclonal antibody (mAb) against the CD8 + dendritic cells (DCs) specific receptor Clec9A to design a nanocarrier emulsion that is able to target Clec9A + DCs; (3) Encapsulation of a model antigen within the immune evading and Clec9A + DCs targeting emulsion to investigate the immune function in a relevant animal model. This work, to our best knowledge, introduces the first DC targeting and immune-evading tailorable nanocarrier emulsion (TNE) made using only biological components and assembled in a bottom-up fashion. Simple topii down sequential addition of immune evading and receptor-specific Ab elements conjugated to DAM...

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The development of stable aqueous suspensions of PEGylated SPIONs for biomedical applications

Cited by 122 publications

References 34 publications

Targeted Magnetic Nanoparticles for Remote Magnetothermal Disruption of Amyloid‐β Aggregates

Targeted Magnetic Nanoparticles for Remote Magnetothermal Disruption of Amyloid‐β Aggregates

Integration of binding peptide selection and multifunctional particles as tool-box for capture of soluble proteins in serum

Tailorable nanocarrier emulsion for drug delivery

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