Engineering tumor-targeted gadolinium hexanedione nanoparticles for potential application in neutron capture therapy

被引:62
作者
Oyewumi, MO [1 ]
Mumper, RJ [1 ]
机构
[1] Univ Kentucky, Ctr Pharmaceut Sci & Technol, Coll Pharm, Div Pharmaceut Sci, Lexington, KY 40536 USA
关键词
D O I
10.1021/bc025560x
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Microemulsions (oil-in-water) have been employed as templates to engineer nanoparticles containing high concentrations of gadolinium for potential application in neutron capture therapy of tumors. Gadolinium hexanedione (GdH), synthesized by complexation of Gd3+ with 2,4-hexanedione, was used as the nanoparticle matrix alone or in combination with either emulsifying wax or PEG-400 monostearate. Solid nanoparticles (<125 nm size) were obtained by simple cooling of the microemulsions prepared at 60 degreesC to room temperature in one vessel. The feasibility of tumor targeting via folate receptors was studied. A folate ligand was synthesized by chemically linking folic acid to distearoyl-phosphatidylethanolamine (DSPE) via a poly(ethylene glycol) (PEG; MW 3350) spacer. To obtain folate-coated nanoparticles, the folate ligand (0.75% w/w to 15% w/w) was added to either the microemulsion templates at 60 degreesC or nanoparticle suspensions at 25 degreesC. Efficiencies of folate ligand attachment/ adsorption to nanoparticle formulations were monitored by gel permeation chromatography. Cell uptake studies were carried out in KB cells (human nasopharyngeal epidermal carcinoma cell line), known to overexpress folate receptors. The uptake of folate-coated nanoparticles was about 10-fold higher than uncoated nanoparticles after 30 min at 37 degreesC. The uptake of folate-coated nanoparticles at 4 degreesC was 20-fold lower than the uptake at 37 degreesC and comparable to the uptake of uncoated nanoparticles at 37 degreesC. Folate-mediated endocytosis was further verified by the inhibition of folate-coated nanoparticles uptake by free folic acid. It was observed that folate-coated nanoparticles uptake decreased to similar to2% of its initial value with the coincubation of 0.001 mM of free folic acid. The results suggested that these tumor-targeted nanoparticles containing high concentrations of Gd may have potential for neutron capture therapy.
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页码:1328 / 1335
页数:8
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