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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

Biomedical Sciences Research Institute Computer Science Research Institute Environmental Sciences Research Institute Nanotechnology & Advanced Materials Research Institute

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
Faculty of Life and Health Sciences > School of Pharmacy and Pharmaceutical Science
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 15:38
Last Modified:26 Nov 2012 11:58

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