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

摘要

A targeted and controlled drug delivery system based on beta-cyclodextrin (beta-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 beta-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 beta-CD in order to rapid release of CUR on targeted cell surface. Fluorescencemicroscopy images and cytotoxicity studies represent significantly greater cellular uptake and anti-proliferative effects of CUR by beta-CD-CUR/MAase-Trastuzumab bioconjugate compared to free CUR and beta-CD-CUR in presence and absence of MAase in HER2 positive cells. The results from flow cytometric assay suggest that the beta-CDCUR/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. (C) 2020 Elsevier B.V. All rights reserved.