title: 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.affiliation: Department of Natural Products Chemistry, Fudan University, Shanghai, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Xie
authors.forename: Jun
authors.initials: J
authors.lastname: Chang
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Hao
authors.forename: Jian-Ming
authors.initials: JM
authors.lastname: Yu
authors.forename: Hong-Rui
authors.initials: HR
authors.lastname: Liu
authors.forename: Xun
authors.initials: X
authors.lastname: Sun
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000473:pathology; D000077143:Docetaxel; D016503:Drug Delivery Systems; D005461:Fluorine / Q000737:chemistry; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000473:pathology; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000378:metabolism; D061848:Optical Imaging; D017239:Paclitaxel / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D011355:Prodrugs; D012235:Rhodamines / Q000737:chemistry; D043823:Taxoids / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D011355:Prodrugs; D012235:Rhodamines; D043823:Taxoids; D000077143:Docetaxel; D005461:Fluorine; C029773:rhodamine B; D017239:Paclitaxel
keywords: Docetaxel; Fluorescence imaging; Mitochondrial-targeted; Prodrug cancer therapy; Prodrug conversion; Rhodamine B