Glucose-installed, SPIO-loaded PEG-b-PCL micelles as MR contrast agents to target prostate cancer cells

Man Theerasilpa,b , Panya Sunintaboonc , Witaya Sungkaratd ,Norased Nasongklaa,b

a Department of Biomedical Engineering, Faculty of Engineering, Mahidol University, 25/25 Puttamonthon 4th Rd, Nakorn Pathom 73170, Thailand

b Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Mahidol University, Bangkok 10400, Thailand

c Department of Chemistry, Faculty of Science, Mahidol University, Nakorn Patom 73170, Thailand

d Department of Radiology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand


Polymeric micelles of poly(ethylene glycol)-block-poly(ɛ-caprolactone) bearing glucose analog encapsulated with superparamagnetic iron oxide nanoparticles (Glu-SPIO micelles) were synthesized as an MRI contrast agent to target cancer cells based on high-glucose metabolism. Compared to SPIO micelles (non-targeting SPIO micelles), Glu-SPIO micelles demonstrated higher toxicity to human prostate cancer cell lines (PC-3) at high concentration. Atomic absorption spectroscopy was used to determine the amount of iron in cells. It was found that the iron in cancer cells treated by Glu-SPIO micelles were 27-fold higher than cancer cells treated by SPIO micelles at the iron concentration of 25 ppm and fivefold at the iron concentration of 100 ppm. To implement Glu-SPIO micelles as a MR contrast agent, the 3-T clinical MRI was applied to determine transverse relaxivities (r 2*) and relaxation rate (1/T 2*) values. In vitro MRI showed different MRI signal from cancer cells after cellular uptake of SPIO micelles and Glu-SPIO micelles. Glu-SPIO micelles was highly sensitive with the r 2* in agarose gel at 155 mM−1 s−1. Moreover, the higher 1/T 2* value was found for cancer cells treated with Glu-SPIO micelles. These results supported that glucose ligand increased the cellular uptake of micelles by PC-3 cells with over-expressing glucose transporter on the cell membrane. Thus, glucose can be used as a small molecule ligand for targeting prostate cancer cells overexpressing glucose transporter.



Keywords:  Drug delivery system; MR contrast agents; Polymeric micelles; Superparamagnetic iron oxide; Targeting nanoparticles


For more details: Applied Nanoscience volume 7pages711–721 (2017).