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

Ronak Savla, Oleh Taratula, Olga Garbuzenko, Tamara Minko

Research output: Contribution to journalArticlepeer-review

231 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)16-22
Number of pages7
JournalJournal of Controlled Release
Volume153
Issue number1
DOIs
StatePublished - Jul 15 2011

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

Keywords

  • Aptamer
  • Doxorubicin
  • Drug delivery
  • Imaging
  • Nanomedicine
  • Quantum dot

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