Degree

Doctor of Philosophy (PhD)

Department

Chemistry

Document Type

Dissertation

Abstract

Second harmonic generation (SHG) is used to investigate the factors that impact nanoparticle-based drug-delivery applications. In the first study, molecular adsorption and transport kinetics of a positively-charged dye, malachite green isothiocyanate (MGITC), is characterized at the surface of different colloidal liposomes in water using SHG spectroscopy. The molecular interactions of MGITC is compared to our previous investigations with malachite green (MG). In comparison to MG, MGITC demonstrates stronger adsorption and faster transport through lipid membranes. Correspondingly, the SHG experimental results are in excellent agreement with the molecular dynamics (MD) simulations results. A key finding illustrates the importance of functional groups, such as isothiocyanate, in controlling molecular translocation across the phospholipid-water interface. In a related study, temperature-dependent SHG measurements are performed to investigate the thermodynamics associated with the adsorption and transport kinetics of MG at the surface of 1,2-dioleoyl-sn-glycero-3phospho-(1’rac-glycerol) (DOPG) liposomes. The molecular transport is determined to be approximately 5 times faster at 40 ⁰C in comparison to the molecular transport at 25 ⁰C. Additionally, the changes in adsorption enthalpy and entropy are determined. The change in adsorption entropy is positive and the change in adsorption enthalpy is negative, indicating that the adsorption process is spontaneous at all aqueous temperatures. Similarly, SHG microscopy is used to probe the molecular interactions of MG and MGITC molecules at the surface of living human nonsmall adenosquamous lung cancer cells (H596 cells). The observed molecular translocation in living H596 cells is significantly faster for MGITC in comparison to MG. SHG microscopy is also used to probe fixed, dead H596 cells with MGITC dye molecules. In comparison to fixed cells, living cells have pronounced fluctuations of SHG intensity which is attributed to more complicated interactions, including active transport and cell regulation. Finally, gold, silver, and gold-silver-gold core-shell-shell (CSS) plasmonic nanoparticles having size of 10-100 nm are synthesized and functionalized with miRNA molecules using Diels-Alder chemistry. The retro Diels-Alder thermal release of miRNA from the surface of novel plasmonic nanoparticles is investigated at their corresponding plasmon resonances using surface-specific SHG spectroscopy. In summary, these time-resolved studies highlight the importance of SHG as a sensitive, powerful, and versatile tool to monitor the real-time surface chemistry of colloidal nanoparticle-based drug-delivery systems.

Date

8-13-2020

Committee Chair

Haber, Louis

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