Selective targeting of antibody-conjugated nanoparticles to leukemic cells and primary T-lymphocytes.
In the present study, surface-modified nanoparticles based on biodegradable material were used for antibody coupling in order to get a selective drug carrier systems. Gelatin nanoparticles were prepared by a desolvation process. Sulfhydryl groups were introduced which enabled the linkage of NeutrAvidin (NAv). Antibodies specific for the CD3 antigen on lymphocytic cells were conjugated to the nanoparticles surface. The binding of biotinylated anti-CD3 antibody was achieved by NAv-biotin-complex formation. Cellular binding and uptake were determined by flow cytometry and confocal laser scanning microscopy (CLSM). Cell-type-specific targeting of anti-CD3-conjugated nanoparticles into CD3-positive human T-cell leukemia cells and primary T-lymphocytes could be shown. Celluar uptake and effective internalization of antibody-conjugated nanoparticles into CD3 expressing cells were demonstrated. Uptake rates of about 84% into T-cell leukemia cells were observed. To confirm selectivity of T-cell targeting, competition experiments were carried out adding excessive free anti-CD3 prior to nanoparticle incubation leading to significantly reduced cellular uptake of antibody-conjugated nanoparticles. Further analysis on the mechanism of uptake confirmed a receptor-mediated endocytotic process. Protein-based nanoparticles conjugated with an antibody against a specific cellular antigen hold promise as selective drug delivery systems for specific cell types.
Dinauer
Norbert
N
Chemotherapeutische Forschungsinstitut Georg-Speyer-Haus, D-60596 Frankfurt, Germany.
Balthasar
Sabine
S
Weber
Carolin
C
Kreuter
Jörg
J
Langer
Klaus
K
von Briesen
Hagen
H
D000906:Antibodies / Q000737:chemistry*; D001360:Avidin / Q000737:chemistry; D001667:Binding, Competitive; D001672:Biocompatible Materials / Q000737:chemistry*; D019921:Biotinylation; D017252:CD3 Complex / Q000096:biosynthesis / Q000737:chemistry; D002460:Cell Line; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D004705:Endocytosis; D005434:Flow Cytometry; D005780:Gelatin / Q000737:chemistry; D006801:Humans; D019169:Jurkat Cells; D007938:Leukemia; D007963:Leukocytes, Mononuclear / Q000166:cytology; D018613:Microscopy, Confocal; D008956:Models, Chemical; D049329:Nanostructures / Q000737:chemistry*; D036103:Nanotechnology; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism
D000906:Antibodies; D001672:Biocompatible Materials; D017252:CD3 Complex; D004337:Drug Carriers; C093483:neutravidin; D001360:Avidin; D005780:Gelatin