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Davide Brambilla,
Romain Verpillot,
Benjamin Le Droumaguet,
Julien Nicolas,
Myriam Taverna,
Juraj Kóňa,
Barbara Lettiero, S Hossein Hashemi,
Line De Kimpe,
Mara Canovi,
Marco Gobbi,
Valérie Nicolas,
Wiep Scheper,
S Moein Moghimi,
Igor Tvaroška,
Patrick Couvreur,
Karine Andrieux
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ABSTRACT: We have demonstrated that the polyethylene glycol (PEG) corona of long-circulating polymeric nanoparticles (NPs) favors interaction with the amyloid-beta (Aβ(1-42)) peptide both in solution and in serum. The influence of PEGylation of poly(alkyl cyanoacrylate) and poly(lactic acid) NPs on the interaction with monomeric and soluble oligomeric forms of Aβ(1-42) peptide was demonstrated by capillary electrophoresis, surface plasmon resonance, thioflavin T assay, and confocal microscopy, where the binding affected peptide aggregation kinetics. The capture of peptide by NPs in serum was also evidenced by fluorescence spectroscopy and ELISA. Moreover, in silico and modeling experiments highlighted the mode of PEG interaction with the Aβ(1-42) peptide and its conformational changes at the nanoparticle surface. Finally, Aβ(1-42) peptide binding to NPs affected neither complement activation in serum nor apolipoprotein-E (Apo-E) adsorption from the serum. These observations have crucial implications in NP safety and clearance kinetics from the blood. Apo-E deposition is of prime importance since it can also interact with the Aβ(1-42) peptide and increase the affinity of NPs for the peptide in the blood. Collectively, our results suggest that these engineered long-circulating NPs may have the ability to capture the toxic forms of the Aβ(1-42) peptide from the systemic circulation and potentially improve Alzheimer's disease condition through the proposed "sink effect".
ACS Nano 06/2012; 6(7):5897-908. · 10.77 Impact Factor
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ABSTRACT: Alzheimer's disease (AD) represents the most common form of dementia worldwide, affecting more than 35 million people. Advances in nanotechnology are beginning to exert a significant impact in neurology. These approaches, which are often based on the design and engineering of a plethora of nanoparticulate entities with high specificity for brain capillary endothelial cells, are currently being applied to early AD diagnosis and treatment. In addition, nanoparticles (NPs) with high affinity for the circulating amyloid-β (Aβ) forms may induce "sink effect" and improve the AD condition. There are also developments in relation to in vitro diagnostics for AD, including ultrasensitive NP-based bio-barcodes, immunosensors, as well as scanning tunneling microscopy procedures capable of detecting Aβ(1-40) and Aβ(1-42). However, there are concerns regarding the initiation of possible NP-mediated adverse events in AD, thus demanding the use of precisely assembled nanoconstructs from biocompatible materials. Key advances and safety issues are reviewed and discussed.
Nanomedicine: nanotechnology, biology, and medicine 04/2011; 7(5):521-40. · 5.44 Impact Factor
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ABSTRACT: Administration of liposome- and polymer-based clinical nanomedicines, as well as many other proposed multifunctional nanoparticles, often triggers hypersensitivity reactions without the involvement of IgE. These anaphylactic reactions are believed to be secondary to activation of the complement system, giving rise to the release of anaphylatoxins C3a and C5a that initiate a wide array of responses through their effect on mast cells, polymorphonuclear cells, platelets and monocytes. Additionally, the terminal complement C5b-9 complex induces platelet activation, thereby enhancing their procoagulant activity, and has the capacity to elicit non-lytic stimulatory responses from vascular endothelial cells. Here we discuss the molecular basis of complement activation by liposomes, including poly(ethylene glycol) coated vesicles, and other related lipid-based and phospholipid-poly(ethylene glycol) conjugate stabilized entities. We have further considered the role of these complement activating entities in experimental oncology since intra-tumoural complement activation is suggested to induce tumour growth and progression.
Journal of Biomedical Nanotechnology 08/2009; 5(4):364-72. · 4.22 Impact Factor
