摘要

Conjugation of folate (FOL) to nanobubbles could enhance the selective targeting to tumors expressing high levels of folate receptor (FR). To further improve the selective targeting ability of FOL-modified nanobubbles, a novel FOL-targeted nanobubble ((FOL)(2)-NB) with increasing FOL content (accomplished by linking two FOL molecules per DSPE-PEG2000 chain) was synthesized, through the methods of mechanical shaking and low-speed centrifugation based on lipid-stabilized perfluoropropane. The bubble size and distribution range were measured by dynamic light scattering (DLS). Enhanced imaging ability was evaluated using a custom-made agarose mold with a clinical US imaging system at mechanical indices of up to 0.12 at a center frequency of 9.0 MHz. Targeted ability was also carried out in human breast cancer MCF-7 cells, which over-express the FR, by fluorescence activated cell sorting (FACS) and fluorescence microscopy, respectively. (FOL)(2)-NB with a particle size of 286.87 +/- 22.96 nm were successfully prepared, and they exhibited superior contrast imaging effect. FACS and fluorescence microscopy studies showed greater cellular targeting ability in the group of (FOL)(2)-NB than in their control group of Non-targeted-NB (no FOL targeted nanobubbles) and FOL-NB (one FOL molecule per DSPE-PEG2000 chain). These results suggest that a new type of stronger targeted nanobubble was successfully prepared by increasing the FOL content per DSPE-PEG2000 chain. This novel (FOL)(2)-NBs are potentially useful for ultrasound molecular imaging and treatment of FR-positive tumors and are worthy for further investigation.