Targeted anticancer prodrug therapy using dextran mediated enzyme-antibody conjugate and β-cyclodextrin-curcumin inclusion complex.

Abstract

A targeted and controlled drug delivery system based on β-cyclodextrin (β-CD) for encapsulation and controlled release of hydrophobic drugs in the presence of maltogenic amylase (MAase), as a cyclodextrin-hydrolyzing enzyme, and trastuzumab antibody has been developed. In this study, the inclusion complex of curcumin (CUR), as a model anticancer compound, with β-CD was prepared and we constructed an antibody-enzyme bioconjugate (dextran mediated MAase-Trastuzumab bioconjugate) for controlled and targeted release of CUR at HER2 positive cancer cells (including SKBR3 and BT474). Immunocytochemistry analysis indicated that the MAase-Trastuzumab bioconjugate had significant binding affinities to HER2 positive cancer cells and demonstrated high enzyme activity to degrade β-CD in order to rapid release of CUR on targeted cell surface. Fluorescence microscopy images and cytotoxicity studies represent significantly greater cellular uptake and anti-proliferative effects of CUR by β-CD-CUR/MAase-Trastuzumab bioconjugate compared to free CUR and β-CD-CUR in presence and absence of MAase in HER2 positive cells. The results from flow cytometric assay suggest that the β-CD-CUR/MAase-Trastuzumab conjugate exhibited higher cytotoxic and apoptotic effects on cancer cells compared to other formulation. We demonstrate that this formulation has a potential application for targeted and controlled release of drugs in cancer therapy with increased therapeutic efficiency.

• Authors: Sahar Roozbehi, Simin Dadashzadeh, Manouchehr Mirshahi, Majid Sadeghizadeh, Reza H Sajedi
• Journal: International journal of biological macromolecules (Int J Biol Macromol) Vol. 160 Pg. 1029-1041 (Oct 01 2020) ISSN: 1879-0003 [Electronic] Netherlands
• PMID: 32479931 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 Elsevier B.V. All rights reserved.

Chemical References

• Antibodies, Monoclonal
• Antineoplastic Agents
• Dextrans
• Drug Carriers
• Enzymes
• Macromolecular Substances
• Prodrugs
• beta-Cyclodextrins
• Curcumin

Topics

• Antibodies, Monoclonal (chemistry)
• Antineoplastic Agents (chemistry)
• Apoptosis
• Cell Line, Tumor
• Curcumin (administration & dosage, chemistry)
• Dextrans (chemistry)
• Drug Carriers (chemistry)
• Drug Delivery Systems
• Drug Liberation
• Enzymes (chemistry)
• Humans
• Hydrophobic and Hydrophilic Interactions
• Immunohistochemistry
• Macromolecular Substances (chemistry)
• Prodrugs (administration & dosage, chemistry)
• Solubility
• beta-Cyclodextrins (chemistry)