TY - JOUR
T1 - The binding affinity of anti-Aβ1-42 MAb-decorated nanoliposomes to Aβ1-42 peptides in vitro and to amyloid deposits in post-mortem tissue
AU - Canovi, Mara
AU - Markoutsa, Eleni
AU - Lazar, Adina N.
AU - Pampalakis, Georgios
AU - Clemente, Carla
AU - Re, Francesca
AU - Sesana, Silvia
AU - Masserini, Massimo
AU - Salmona, Mario
AU - Duyckaerts, Charles
AU - Flores, Orfeu
AU - Gobbi, Marco
AU - Antimisiaris, Sophia G.
PY - 2011/8
Y1 - 2011/8
N2 - 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.
AB - 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.
KW - Affinity
KW - Alzheimer disease (AD)
KW - Amyloid beta (Aβ)
KW - Antibody
KW - Liposomes
KW - Surface plasmon resonance (SPR)
UR - http://www.scopus.com/inward/record.url?scp=79956323181&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79956323181&partnerID=8YFLogxK
U2 - 10.1016/j.biomaterials.2011.04.020
DO - 10.1016/j.biomaterials.2011.04.020
M3 - Article
C2 - 21529932
AN - SCOPUS:79956323181
VL - 32
SP - 5489
EP - 5497
JO - Biomaterials
JF - Biomaterials
SN - 0142-9612
IS - 23
ER -