Immunocolloidal Targeting of the Endocytotic Siglec-7 Receptor Using Peripheral Attachment of Siglec-7 Antibodies to Poly(Lactide-co-Glycolide) Nanoparticles
Data(s) |
01/01/2008
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Resumo |
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<br/>translocate into cytoplasm by siglec receptor-mediated internalisation.<br/><br/>Materials and Methods: Antibodies to the siglec-7 (CD33-like) receptor were conjugated to dye-loaded nanoparticles using carbodiimide chemistry, giving 32.6 mg 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.<br/><br/>Results: Mouse embryonic fibroblasts expressing recombinant siglec-7 receptor and exposed to NileRed-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.<br/><br/>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<br/>space and delivery drugs intracellularly to cells expressing CD33-like receptors, such as natural killer cells and monocytes. |
Identificador |
http://dx.doi.org/10.1007/s11095-007-9400-7 http://www.scopus.com/inward/record.url?scp=38049178647&partnerID=8YFLogxK |
Idioma(s) |
eng |
Direitos |
info:eu-repo/semantics/restrictedAccess |
Fonte |
Scott , C J , Marouf , W M , Quinn , D J , Buick , R J , Orr , S J , Donnelly , R F & McCarron , P A 2008 , ' Immunocolloidal Targeting of the Endocytotic Siglec-7 Receptor Using Peripheral Attachment of Siglec-7 Antibodies to Poly(Lactide-co-Glycolide) Nanoparticles ' Pharmaceutical Research , vol 25 , no. 1 , pp. 135-146 . DOI: 10.1007/s11095-007-9400-7 |
Palavras-Chave | #/dk/atira/pure/subjectarea/asjc/1600 #Chemistry(all) #/dk/atira/pure/subjectarea/asjc/3000/3003 #Pharmaceutical Science #/dk/atira/pure/subjectarea/asjc/3000/3004 #Pharmacology |
Tipo |
article |