UCLA

This dissertation makes contributions to the fields of functionalized mesoporous silica nanoparticles (MSNs) designed for magnetic resonance imaging (MRI) contrast enhancement and high-intensity focused ultrasound (HIFU) triggered cargo release. MRI-guided HIFU (MRIgHIFU) has been applied as a therapeutic tool in the clinic, and enhanced MRI contrast will improve the precision and applicability of HIFU therapy. In Chapter 2, the ultrasound responsive MSNs carriers are reviewed. In Chapter 3, the proof-of-concept spotlight technique based on MRIgHIFU and MSNs is introduced. With periodic HIFU modulation, the functionalized MSNs generated reversible MRI T1 relaxivity changes at the 1.5 mm3 focal point. Fourier analysis was used to extract signal changes at the modulation frequency, and a modulation enhancement map spotlights the precise region of interest by increasing contrast almost 100-fold. In Chapter 4, another functionalized MSNs were designed for the spotlight technique, and the spectral analysis was further studied to maximize the contrast enhancement. In particular, a framework was presented to analyze the trade-offs between different parameter choices for the signal processing method. In Chapter 5, the application of the spotlight technique was demonstrated at human body temperature. The MSNs were functionalized with the tailored poly(2-oxazoline)s with a lower critical solution temperature (LCST) at 40 �C, so that it could generate reversible MRI contrast change at human body temperature. The temperature oscillation range was small (3 �C), and the data acquisition was relatively fast (in 100 s), which made it a step closer to the biomedical applications in the clinic. The HIFU-responsive cargo delivery was studied in Chapters 6 and 7. The large pore MSNs (LPMSNs) were studied as the nanocarriers to load a large drug molecule, Docetaxel. With the loading procedure and HIFU parameters tuned, the HIFU-responsive release was demonstrated in a biologically relevant solvent. HIFU-responsive MRI contrast agent delivery was studied using MSNs capped with thermo-responsive polymer. The cargo loading and release conditions were optimized, and the HIFU-responsive cargo release can be monitored by MRI contrast change. The spotlight technique in this dissertation is promising for biomedical applications of precision therapy. The framework on parameter choice and demonstrated MRI contrast enhancement at human body temperature provides the foundation for further clinical translation.