Mitochondrial-targeted prodrug cancer therapy using a rhodamine B labeled fluorinated docetaxel.

Abstract

The aim of this work was to track the distribution and conversion of paclitaxel based prodrug by fluorescence imaging, which would help to up-regulate the therapeutic efficacy and reduce cytotoxicity of paclitaxel and docetaxel. We developed a novel prodrug for tumor treatment, in which a fluorinated docetaxel derivative, 4FDT as a chemotherapeutic reagent and rhodamine B as an imaging reporter as well as targeting domain were conjugated via a biodegradable ester bond. In vitro image studies demonstrated the morphological changes of tubulin and chromosomal alterations of human liver cancer cells HepG2, which were similar to the phenomena observed after treatment with the active drug 4FDT. At 48 h post-treatment, the cytotoxicity of 4FDT-RhB was 18.5% of that of 4FDT. However, this value increased to 49.3% of 4FDT at 72 h post-incubation. These experimental results implied the consistent release of the active drug from the prodrug throughout the incubation period via the linear increase in the cytotoxicity observed as a function of time. It also showed good stability in both plasma and complete blood. Additionally, the specific delivery of the prodrug to mitochondria was observed by fluorescent microscopy.

• Authors: Cheng Xie, Jun Chang, Xiao-Dong Hao, Jian-Ming Yu, Hong-Rui Liu, Xun Sun
• Journal: European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V (Eur J Pharm Biopharm) Vol. 85 Issue 3 Pt A Pg. 541-9 (Nov 2013) ISSN: 1873-3441 [Electronic] Netherlands
• PMID: 23791719 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013. Published by Elsevier B.V.

Chemical References

• Antineoplastic Agents
• Antineoplastic Agents, Phytogenic
• Prodrugs
• Rhodamines
• Taxoids
• Docetaxel
• Fluorine
• rhodamine B
• Paclitaxel

Topics

• Antineoplastic Agents (administration & dosage, pharmacokinetics, pharmacology)
• Antineoplastic Agents, Phytogenic (administration & dosage, pharmacokinetics, pharmacology)
• Carcinoma, Hepatocellular (drug therapy, pathology)
• Docetaxel
• Drug Delivery Systems
• Fluorine (chemistry)
• Hep G2 Cells
• Humans
• Liver Neoplasms (drug therapy, pathology)
• Microscopy, Fluorescence
• Mitochondria (metabolism)
• Optical Imaging
• Paclitaxel (administration & dosage, pharmacokinetics, pharmacology)
• Prodrugs
• Rhodamines (chemistry)
• Taxoids (administration & dosage, pharmacokinetics, pharmacology)
• Time Factors