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Actively targeted cetuximab conjugated γ-poly(glutamic acid)-docetaxel nanomedicines for epidermal growth factor receptor over expressing colon cancer cells

Publication Type : Journal Article

Thematic Areas : Nanosciences and Molecular Medicine

Publisher : Journal of Biomedical Nanotechnology

Source : Journal of Biomedical Nanotechnology, American Scientific Publishers, Volume 10, Number 8, p.1416-1428 (2014)

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Keywords : Amino acids, animal cell, Animals, Annexins, Antibodies, Antineoplastic Agents, antiproliferative activity, apoptosis, article, Benzimidazoles, blood compatibility, cancer cell line, Carbocyanines, cell cycle, Cell death, cell viability, cellular distribution, Cetuximab, Colon cancer, Colonic Neoplasms, confocal microscopy, controlled study, cytotoxicity, Diseases, docetaxel, Drug Carriers, drug conjugation, drug efficacy, drug elimination, drug release, drug uptake, Epidermal Growth Factor, epidermal growth factor receptor, Epidermal growth factor receptors, flow cytometry, G2 phase cell cycle checkpoint, gene overexpression, glutamic acid, Hemolysis, HT29 Cells, Humanized, Humans, hydrophilicity, hydrophobicity, infrared spectroscopy, M phase cell cycle checkpoint, Magnesium printing plates, male, Mice, mitochondrial membrane potential, Monoclonal, mouse, MTT assay, nanoencapsulation, nanomedicine, Nanomedicines, nanoparticle, Nanoparticles, near infrared spectroscopy, nonhuman, particle size, polyglutamic acid, Receptor, scanning electron microscopy, Taxoids, tissue distribution, zeta potential

Campus : Kochi

School : Center for Nanosciences

Center : Nanosciences

Department : Nanosciences and Molecular Medicine

Year : 2014

Abstract : Receptor targeted therapy is advantageous in overcoming the toxicity burden of conventional cancer chemotherapeutics. Over expression of epidermal growth factor receptor (EGFR) on cancer cells and its role in metastasis, malignancy and drug resistance in many human cancers lead to its selection as a promising target for cancer treatment. The present work investigated the preparation and characterization of docetaxel (DTXL) loaded γ-poly (glutamic acid) (γ-PGA) nanoparticles (Nps) conjugated with EGFR antibody (Cetuximab, CET) targeted to colon cancer cells (HT-29), highly over expressing EGFR. The flow cytometric analysis revealed two fold increased cellular uptake of CET-DTXL-γ-PGA Nps by HT-29 (EGFR +ve) cells compared to that of IEC-6 (EGFR-ve) cells confirming the active targeting. Cytotoxicity assays (MTT and LDH) showed superior anti-proliferative activity of CET-DTXL-γ-PGA NPs over DTXL-γ-PGA Nps against HT-29 cells. The cell cycle analysis indicated that CET-DTXL-γ-PGA NPs induced cell death in enhanced percentage of HT-29 cells by undergoing cell cycle arrest in G2/M phase compared to that of DTXL-γ-PGA Nps. The mechanism of cancer cell death was analyzed via apoptotic and mitochondrial membrane potential assays and showed that targeted Nps treatment reduced the mitochondrial membrane potential thereby inducing enhanced HT-29 cell death (apoptosis and necrosis). The biodistribution of targeted and non-targeted Nps were analyzed in vivo in Swiss albino mice using NIR imaging. ICG-CET-DTXL-γ-PGA Nps (targeted) and ICG-DTXL-γ-PGA Nps (non-targeted) followed the similar biodistribution pattern in vivo, but with different elimination time. In short, CET-DTXL-γ-PGA nanoparticles enhance the tumor selective therapeutic efficacy for colon cancer. Copyright © 2014 American Scientific Publishers All rights reserved.

Cite this Research Publication : Sa Maya, Sarmento, Bbc d, Lakshmanan, V. - Ka, Menon, Da, and Jayakumar, Ra, “Actively targeted cetuximab conjugated γ-poly(glutamic acid)-docetaxel nanomedicines for epidermal growth factor receptor over expressing colon cancer cells”, Journal of Biomedical Nanotechnology, vol. 10, pp. 1416-1428, 2014.

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