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J Control Release. 2011 Jul 15;153(1):16-22. doi: 10.1016/j.jconrel.2011.02.015. Epub 2011 Feb 20.

Tumor targeted quantum dot-mucin 1 aptamer-doxorubicin conjugate for imaging and treatment of cancer.

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  • 1Department of Pharmaceutics, Rutgers, The State University of New Jersey, Piscataway, NJ 08854-8020, USA.

Abstract

In this study, we report the design and delivery of a tumor-targeted, pH-responsive quantum dot-mucin1 aptamer-doxorubicin (QD-MUC1-DOX) conjugate for the chemotherapy of ovarian cancer. To achieve active cancer targeting, QD was conjugated with a DNA aptamer specific for mutated MUC1 mucin overexpressed in many cancer cells including ovarian carcinoma. DOX was attached to QD via a pH-sensitive hydrazone bond in order to provide the stability of the complex in systemic circulation and drug release in acidic environment inside cancer cells. The data show that this bond is stable at neutral and slightly basic pH and undergoes rapid hydrolysis in mildly acidic pH. Confocal microscopy and in vivo imaging studies show that the developed QD-MUC1-DOX conjugate had higher cytotoxicity than free DOX in multidrug resistant cancer cells and preferentially accumulated in ovarian tumor. Data obtained demonstrate a high potential of the proposed conjugate in treatment of multidrug resistant ovarian cancer.

Copyright © 2011 Elsevier B.V. All rights reserved.

PMID:
21342659
[PubMed - indexed for MEDLINE]
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