Journal
ONCOTARGET
Volume 5, Issue 11, Pages 3622-3635Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.1969
Keywords
Docosahexaenoic acid; Near-infrared imaging; Tumor targeting; Phosphatidylethanolamine; Gemcitabine; tumor therapy
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Funding
- Natural Science Foundation Committee of China [NSFC 81220108012, 61335007, 81371684, 81000666, 81171395, 81328012]
- US National 436 Institutes of Health [R21 EB0155091-01]
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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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