Mi ChenFollow

Degree

Doctor of Philosophy (PhD)

Department

Department of Chemistry

Document Type

Dissertation

Abstract

Recent advances in development of nanomaterials have provided great opportunities for cancer research. In this dissertation, nanoGUMBOS derived from a group of uniform materials based on organic salts (GUMBOS) were investigated for several biomedical applications including chemotherapy, photothermal therapy (PTT), and drug delivery. GUMBOS are solid-phase organic salts consisting of bulky cations and anions. Similar to ionic liquids, GUMBOS display highly tunable properties with counter-ions variation, but with a defined melting point range of 25–250 °C. Nanomaterials derived from GUMBOS, i.e. nanoGUMBOS, display enhanced properties at the nanoscale level. This dissertation focuses on development of near infrared IR780 nanoGUMBOS for biomedical applications.

Firstly, several IR780-based GUMBOS were synthesized and characterized with tunable physicochemical properties. Using hydrophobic properties of these GUMBOS, nanoGUMBOS were directly prepared using a reprecipitation method. Examination of in vitro cytotoxicity indicated enhanced selective toxicity of nanoGUMBOS towards cancer cells with minimum toxicity towards normal cells, as compared to traditional IR780. Results from this study demonstrate that simple counter-ion variation can enhance chemotherapeutic effects.

Encouraged by promising in vitro chemotherapeutic properties of IR780-based nanoGUMBOS, extensive studies using cyclodextrin(CD)-based IR780 nanoGUMBOS for chemo/photothermal antitumor effects were explored. Such nanoGUMBOS displayed several enhanced physical, chemical, and biological properties as compared to nanoGUMBOS without CD. Most importantly, remarkable chemo/photothermal therapeutic effects were observed for CDbased IR780 nanoGUMBOS both in vitro and in vivo.

Finally, a PEGylation approach was employed for fabricating PEGylated IR780-based nanoGUMBOS as multifunctional drug carriers. Herein, a hydrophobic anticancer drug, paclitaxel (PTX), was loaded into nanoGUMBOS for evaluation of their capability for drug delivery. Intriguingly, GUMBOS with greater hydrophobicity resulted in formation of nanoGUMBOS with higher drug loading and more sustained drug release. In vitro cytotoxicity studies indicated significantly enhanced anticancer activity for PTX-loaded nanoGUMBOS as compared to free PTX. Thus, these results confirm efficient delivery of PTX to cancer cells. Moreover, these nanoGUMBOS displayed intense fluorescence emission in the near infrared region, selective toxicity towards cancer cells, and mitochondria targeting properties, thus confirming the multifunctionality of naoGUMBOS. These results suggest a promising approach through simultaneous use of GUMBOS and PEGylation to develop multifunctional nanocarriers.

Committee Chair

Warner, Isiah

DOI

10.31390/gradschool_dissertations.4981

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