Synthesis and optimization of nanoparticles for therapeutic and diagnostic applications

Cancer is currently the second leading cause of death in the United States. There are innumerable avenues being investigated to improve upon current diagnostic and therapeutic platforms, including nanoparticle-based solutions. In this study we investigate potential modifications to the synthesis of a current, widely utilized drug delivery platform and their effects on the resulting characteristics. Doxorubicin liposome of increased diameters and more positive zeta potentials is effectively synthesized as reported by dynamic light scattering (DLS). Encapsulation efficiency of up to 95% is indicated via fluorescence intensity measurement. Attempts to alter surface PEGylation are unable to be detected through differential scanning calorimetry (DSC). Doxorubicin liposomes are generally successfully modified to produce alternative characteristics. In addition we explore novel polymeric nanoparticles for drug delivery. Polytyrosine (PTR) characteristics, such as zeta potential, are found to vary between subsequent preparations via DLS analysis. Stemming from this, variations in cytotoxicity are observed via alamarBlueRTM assay. Shifts in capacity for fluorescent probe delivery are observed with flow cytometry. The issues of batch-batch variation are explored with PTR polymeric nanoparticles. Finally a novel nanotube is explored for potential theranostic applications as a platform for drug delivery, biomarker detection, and magnetic resonance (MR) imaging. Manganese (IV) oxide (MnO2) nanotubes successfully deliver ssDNA for biomarker detection as detected by confocal microscopy and flow cytometry. Successful reduction of MnO2 to Mn2+ is observed for MR imaging applications with moderate T1 relaxivity. Efforts to deliver siRNA targetting MCL-1 are enacted but are unable to be confirmed via quantitative reverse transcription polymerase chain reaction (qRT-PCR). MnO2 nanotubes are successfully applied as platforms for fluorescent biomarker detection and potential application as an MR imaging contrast agent and drug delivery platform are examined.