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Immunocolloidal targeting of the endocytotic siglec-7 receptor using peripheral attachment of siglec-7 antibodies to poly(lactide-co-glycolide) nanoparticles

Scott, C. J., Marouf, W. M., Quinn, D. J., Buick, R. J., Orr, S. J., Donnelly, R. F. and McCarron, Paul (2008) Immunocolloidal targeting of the endocytotic siglec-7 receptor using peripheral attachment of siglec-7 antibodies to poly(lactide-co-glycolide) nanoparticles. Pharmaceutical research, 25 (1). pp. 135-146. [Journal article]

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Abstract

Purpose. To prepare a nanoparticulate formulation expressing variable peripheral carboxyl density using non-endcapped and endcapped poly(lactide-co-glycolide), conjugated to antibodies recognising the siglec-7 receptor, which is expressed on most acute myeloid leukaemias. The aim is to exploit this receptor as a therapeutic target by constructing an internalising drug-loaded nanoparticle able to translocate into cytoplasm by siglec receptor-mediated internalisation. Materials and Methods. Antibodies to the siglec-7 (CD33-like) receptor were conjugated to dye-loaded nanoparticles using carbodiimide chemistry, giving 32.6 mu g protein per mg of nanoparticles using 100% of the non-endcapped PLGA. Binding studies using cognate antigen were used to verify preservation of antibody function following conjugation. Results. Mouse embryonic fibroblasts expressing recombinant siglec-7 receptor and exposed to Nile-Red-loaded nanoparticles conjugated to antibody accumulated intracellular fluorescence, which was not observed if either antibody or siglec-7 receptor was absent. Confocal microscopy revealed internalised perinuclear cytoplasmic staining, with an Acridine Orange-based analysis showing red staining in localised foci, indicating localisation within acidic endocytic compartments. Conclusions. Results show antibody-NP constructs are internalised via siglec-7 receptor-mediated internalisation. If loaded with a therapeutic agent, antibody-NP constructs can cross into cytoplasmic space and delivery drugs intracellularly to cells expressing CD33-like receptors, such as natural killer cells and monocytes.

Item Type:Journal article
Faculties and Schools:Faculty of Life and Health Sciences > School of Pharmacy and Pharmaceutical Science
Faculty of Life and Health Sciences
Research Institutes and Groups:Biomedical Sciences Research Institute
Biomedical Sciences Research Institute > Pharmaceutical Science and Practice
ID Code:1177
Deposited By: Professor Paul McCarron
Deposited On:21 Sep 2010 14:38
Last Modified:26 Nov 2012 11:58

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