Targeting an Ultrasound Contrast Agent to Folate Receptors on Ovarian Cancer Cells

摘要

Objective. The purpose of the study was to synthesize and characterize folate‐targeted microbubbles (MB_(F)) as an ultrasound contrast agent and to evaluate their affinity to the folate receptor (FR) in vitro. Methods. Folate‐targeted microbubbles were prepared by incorporating 1,2‐distearoyl‐sn‐glycero‐3‐phosphoethanolamine‐N ‐[amino(polyethylene glycol)‐2000]‐folate into the lipid membrane of microbubbles. The diameter and concentration of the MB_(F) were determined by a cell counter and sizer. The MB_(F), control microbubbles (MB_(C)), and MB_(F) with a free folic acid block‐ade were tested for binding specificity to human ovarian carcinoma SKOV3 cells, which overexpress the FR, by microscopy and confocal imaging, respectively. Results. The basic physical characteristics of MB_(F) were similar to those of MB_(C). In the cell binding test, the adherence efficiency of MB_(F) to the SKOV3 cells (mean ± SD, 16 ± 5 microbubbles per cell; P & .01) was significantly higher than that of MB_(C) (0.7 ± 0.4 microbubbles per cell) or MB_(F) with the free folic acid blockade (0.7 ± 0.6 microbubbles per cell). Conclusions. Folate‐targeted microbubbles showed high affinity to SKOV3 cells with FR overexpression. They are potentially useful for ultrasonic molecular imaging and treatment of FR‐positive tumors and warrant further investigation.