The targeting mechanism of DHA ligand and its conjugate with Gemcitabine for the enhanced tumor therapy
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Siwen Li1, Jingyi Qin1, Caiping Tian1, Jie Cao1, Guissi Fida1, Zhaohui Wang1, Haiyan Chen1, Zhiyu Qian2, Wei R Chen3, Yueqing Gu1
1 Department of Biomedical Engineering, State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University
2 Department of Biomedical Engineering, School of Automation, Nanjing University of Aeronautics and Astronautics, Nanjing, China
3 Department of Engineering and Physics, University of Central Oklahoma, Edmond, Oklahoma
Yueqing Gu, email:
Keywords: Docosahexaenoic acid, Near-infrared imaging, Tumor targeting, Phosphatidylethanolamine, Gemcitabine, tumor therapy
Received: March 27, 2014 Accepted: May 12, 2014 Published: May 13, 2014
Docosahexaenoic acid (DHA), an omega-3 C22 natural fatty acid serving as a precursor for metabolic and biochemical pathways, was reported as a targeting ligand of anticancer drugs. However, its tumor targeting ability and mechanism has not been claimed. Here we hypothesized that the uptake of DHA by tumor cells is related to the phosphatidylethanolamine (PE) contents in cell membranes. Thus, in this manuscript, the tumor-targeting ability of DHA was initially demonstrated in vitro and in vivo on different tumor cell lines by labeling DHA with fluorescence dyes. Subsequently, the tumor targeting ability was then correlated with the contents of PE in cell membranes to study the uptake mechanism. Further, DHA was conjugated with anticancer drug gemcitabine (DHA-GEM) for targeted tumor therapy. Our results demonstrated that DHA exhibited high tumor targeting ability and PE is the main mediator, which confirmed our hypothesis. The DHA-GEM displayed enhanced therapeutic efficacy than that of GEM itself, indicating that DHA is a promising ligand for tumor targeted therapy.
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