UCLA

Nanocarriers that localize a therapeutic to a disease site and release it “on-demand” via the clinician’s control will mitigate the adverse effects that reduce a patient’s quality of life while undergoing oncology treatment. Moreover, magnetically actuated drug delivery carriers are appealing platforms in next-generation targeted medicine, yet these carriers must be compatible with scalable fabrication techniques to realize their clinical translation. In this dissertation, a magnetically capped porous silicon nanocomposite (APTESPSi@Fe3O4), that responds to physiologically relevant temperatures, was developed using cost-effective, highly scalable methods such as electrochemical etching. Fourier transform infrared spectroscopy (FTIR), CHNS elemental analysis, and zeta potential confirmed that accelerated hydrolysis at 45 �C altered the porous silicon surface chemistry. This hydrolysis-mediated electrostatic degradation between the porous silicon and Fe3O4 caps translated to a thermoresponsive release behavior in dissolution studies with sorafenib (SFN), where minimal drug was released at room temperature and 37 �C, while an enhanced release occurred at 45 �C and 50 �C. The magnetic heat dissipation capabilities with application of an alternating magnetic field (AMF) was calculated by the specific absorption rate (SAR) through calorimetry and magnetic susceptibility measurements. Comparing these two methods revealed that the electrostatic interactions between the porous silicon and Fe3O4 do not hinder the Brownian relaxation and heat dissipation. The nanocomposite and its components demonstrated high cytocompatibility after 24 hours with RAW 246.7, MDA-MB-231, and HepG2 cells, but not with MCF-7. High cytocompatibility was also observed when the cells incubated with particles were heated to 45 �C for 15 min followed by 37 �C for the remaining 6 hour incubation period. Porous silicon and its nanocomposite improved the SFN solubility in in vitro studies with MDA-MB-231 and HepG2, resulting in increased anticancer activity in comparison to the free drug. Moreover, the anticancer activity was readily controlled from the magnetic nanocomposite by modulating the amount of SFN released with temperature. Confocal microscopy and flow cytometry showed a higher uptake of the amine-modified porous silicon in comparison to the magnetic nanocomposite in MDA-MB-231 cells. The temperature increase to 45 �C showed a reduced particle uptake, yet future studies monitoring the fluorescence from the free drug rather than the nanocarrier will prove useful. This novel system has laid the groundwork for a promising tool for clinicians to lessen the burden that millions of cancer patients face as they receive treatment.