Targeting cancer cells using PLGA nanoparticles surface modified with monoclonal antibody

• Published in: Journal of controlled release 2007-07, Vol.120 (1), p.18-26
• Main Authors: Kocbek, Petra, Obermajer, Nataša, Cegnar, Mateja, Kos, Janko, Kristl, Julijana
• Format: Article
• Language: English
• Subjects: Active targeting; Antibodies, Monoclonal - chemistry; Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - metabolism; Antibody Specificity; Antigens, Neoplasm - immunology; Antigens, Neoplasm - metabolism; Biological and medical sciences; Breast Neoplasms - immunology; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Caco-2 Cells; Cell co-culture; Cell Membrane - metabolism; Coculture Techniques; Drug Carriers; Female; Flow Cytometry; Fluorescein - metabolism; Fluorescence Resonance Energy Transfer; Fluorescent Dyes - metabolism; General pharmacology; Humans; Keratins - immunology; Keratins - metabolism; Lactic Acid - chemical synthesis; Lactic Acid - chemistry; Lactic Acid - metabolism; Medical sciences; Microscopy, Fluorescence; Monoclonal antibody; Nanoparticles; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; PLGA; Polyglycolic Acid - chemical synthesis; Polyglycolic Acid - chemistry; Polyglycolic Acid - metabolism; Polymers - chemical synthesis; Polymers - chemistry; Polymers - metabolism; Surface Plasmon Resonance
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2007.03.012

Targeting drugs to their sites of action is still a major challenge in pharmaceutical research. In this study, polylactic-co-glycolic acid (PLGA) immuno-nanoparticles were prepared for targeting invasive epithelial breast tumour cells. Monoclonal antibody (mAb) was used as a homing ligand and was attached to the nanoparticle surface either covalently or non-covalently. The presence of mAb on the nanoparticle surface, its stability and recognition properties were tested. Protein assay, surface plasmon resonance, flow cytometry and fluorescence-immunostaining confirmed the presence of mAb on nanoparticles in both cases. However, a binding assay using cell lysate revealed that the recognition properties were preserved only for nanoparticles with adsorbed mAb. These nanoparticles were more likely to be bound to the targeted cells than non-coated nanoparticles. Both types of nanoparticles entered the target MCF-10A neoT cells in mono-culture. In co-culture of MCF-10A neoT and Caco-2 cells immuno-nanoparticles were localized solely to MCF-10A neoT cells, whereas non-coated nanoparticles were distributed randomly. Immuno-nanoparticles entered only MCF-10A neoT cells, while non-coated nanoparticles were taken up by both cell types, indicating specific targeting of the immuno-nanoparticles. In conclusion, we demonstrate a method by which mAbs can be bound to nanoparticles without detriment to their targeting ability. Furthermore, the results show the effectiveness of the new carrier system for targeted delivery of small or large active substances into cells or tissues of interest.