The binding affinity of anti-Aβ1-42 MAb-decorated nanoliposomes to Aβ1-42 peptides in vitro and to amyloid deposits in post-mortem tissue

Mara Canovi, Eleni Markoutsa, Adina N. Lazar, Georgios Pampalakis, Carla Clemente, Francesca Re, Silvia Sesana, Massimo Masserini, Mario Salmona, Charles Duyckaerts, Orfeu Flores, Marco Gobbi, Sophia G. Antimisiaris

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Amyloid β (Aβ) aggregates are considered as possible targets for therapy and/or diagnosis of Alzheimer disease (AD), and nanoparticles functionalized with Aβ-specific ligands are considered promising vehicles for imaging probes and therapeutic agents. Herein, we characterized the binding properties of nanoliposomes decorated with an anti-Aβ monoclonal antibody (Aβ-MAb). The Aβ-MAb was obtained in mice by immunization with Aβ antigen followed by hybridoma fusion. Surface Plasmon Resonance (SPR) studies confirmed the very high affinity of purified Aβ-MAb for both Aβ monomers and fibrils (KD = 0.08 and 0.13 nm, respectively). The affinity of the biotinylated Aβ-MAb, used thereafter for liposome decoration, was lower although still in the low nanomolar range (KD = 2.1 and 1.6 nm, respectively). Biotin-streptavidin ligation method was used to decorate nanoliposomes with Aβ-MAb, at different densities. IgG-decorated liposomes were generated by the same methodology, as control. Vesicles were monodisperse with mean diameters 124-134 nm and demonstrated good colloidal stability and integrity when incubated with serum proteins. When studied by SPR, Aβ-MAb-liposomes, but not IgG-liposomes, markedly bound to Aβ monomers and fibrils, immobilized on the chip. KD values (calculated on Aβ-MAb content) were about 0.5 and 2 nm with liposomes at high and low Aβ-MAb density, respectively. Aβ-MAb-liposome binding to Aβ fibrils was additionally confirmed by ultracentrifugation technique, in which interactions occur in solution under physiological conditions. Moreover, Aβ-MAb-liposomes bound amyloid deposits in post-mortem AD brain samples, confirming the potential of these nanoparticles for the diagnosis and therapy of AD.

Original languageEnglish
Pages (from-to)5489-5497
Number of pages9
JournalBiomaterials
Volume32
Issue number23
DOIs
Publication statusPublished - Aug 2011

Fingerprint

Monoclonal antibodies
Amyloid Plaques
Amyloid
Peptides
Liposomes
Deposits
Monoclonal Antibodies
Tissue
Alzheimer Disease
Surface Plasmon Resonance
Surface plasmon resonance
Nanoparticles
Immunoglobulin G
Monomers
In Vitro Techniques
Immunization
Streptavidin
Ultracentrifugation
Hybridomas
Antigens

Keywords

  • Affinity
  • Alzheimer disease (AD)
  • Amyloid beta (Aβ)
  • Antibody
  • Liposomes
  • Surface plasmon resonance (SPR)

ASJC Scopus subject areas

  • Biomaterials
  • Bioengineering
  • Ceramics and Composites
  • Mechanics of Materials
  • Biophysics

Cite this

Canovi, M., Markoutsa, E., Lazar, A. N., Pampalakis, G., Clemente, C., Re, F., ... Antimisiaris, S. G. (2011). The binding affinity of anti-Aβ1-42 MAb-decorated nanoliposomes to Aβ1-42 peptides in vitro and to amyloid deposits in post-mortem tissue. Biomaterials, 32(23), 5489-5497. https://doi.org/10.1016/j.biomaterials.2011.04.020

The binding affinity of anti-Aβ1-42 MAb-decorated nanoliposomes to Aβ1-42 peptides in vitro and to amyloid deposits in post-mortem tissue. / Canovi, Mara; Markoutsa, Eleni; Lazar, Adina N.; Pampalakis, Georgios; Clemente, Carla; Re, Francesca; Sesana, Silvia; Masserini, Massimo; Salmona, Mario; Duyckaerts, Charles; Flores, Orfeu; Gobbi, Marco; Antimisiaris, Sophia G.

In: Biomaterials, Vol. 32, No. 23, 08.2011, p. 5489-5497.

Research output: Contribution to journalArticle

Canovi, M, Markoutsa, E, Lazar, AN, Pampalakis, G, Clemente, C, Re, F, Sesana, S, Masserini, M, Salmona, M, Duyckaerts, C, Flores, O, Gobbi, M & Antimisiaris, SG 2011, 'The binding affinity of anti-Aβ1-42 MAb-decorated nanoliposomes to Aβ1-42 peptides in vitro and to amyloid deposits in post-mortem tissue', Biomaterials, vol. 32, no. 23, pp. 5489-5497. https://doi.org/10.1016/j.biomaterials.2011.04.020
Canovi, Mara ; Markoutsa, Eleni ; Lazar, Adina N. ; Pampalakis, Georgios ; Clemente, Carla ; Re, Francesca ; Sesana, Silvia ; Masserini, Massimo ; Salmona, Mario ; Duyckaerts, Charles ; Flores, Orfeu ; Gobbi, Marco ; Antimisiaris, Sophia G. / The binding affinity of anti-Aβ1-42 MAb-decorated nanoliposomes to Aβ1-42 peptides in vitro and to amyloid deposits in post-mortem tissue. In: Biomaterials. 2011 ; Vol. 32, No. 23. pp. 5489-5497.
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