We developed a new technique for externally controlled on-command magnetic resonance (MR) imaging contrast enhancement using an MR-guided high intensity focused ultrasound (MRgHIFU)-stimulated cargo delivery strategy with minimal bulk heating. The Gd-based MR contrast agent Gd(DTPA)2- was used as the cargo in polymer-coated mesoporous silica nanoparticles (MSNs) nanocarriers. The polyethylene glycol-based polymer served as an ultrasound-sensitive cap that regulated the controlled release of Gd(DTPA)2- from MSNs when triggered by ultrasound. Gel phantom experiments and an ex-vivo study in chicken breasts were performed to demonstrate the controlled MR image contrast enhancement with less than 10 °C of bulk heating. This approach is advantageous in several aspects. First, the polymer is biocompatible and effectively stabilizes the particles’ dispersion in physiological environment. Second, the release of Gd(DTPA)2- was spatiotemporally and quantitatively controlled by HIFU and monitored by MRI. Third, the polymer is mainly responsive to mechanical forces, so that Gd(DTPA)2- could be efficiently released from MSNs at low temperature (temperature rise no more than 4 °C) during ultrasound stimulation. Finally, the amount of Gd(DTPA)2- released from MSNs was regulated by the ultrasound stimulation power level, duration per cycle, and number of cycles. The amount of released Gd(DTPA)2- was characterized by measuring changes in T1-weighted image intensity and T1 relaxation time before and after ultrasound stimulation. This ultrasound controlled on-command cargo delivery strategy was applied to deliver an anticancer drug to ovarian cancer cells and greatly enhanced the cell killing efficiency compared with that of the free drug itself. This new technique showing on-command MR imaging contrast enhancement and drug delivery opens up an opportunity for future image-guided theranostic applications.

Ultrasound-stimulated cargo release at low temperature for spatiotemporally and quantitatively controllable contrast enhancement by magnetic resonance guided high intensity focused ultrasound

2019 Fall National Meeting

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