Date of Degree

9-2016

Document Type

Dissertation

Degree Name

Ph.D.

Program

Chemistry

Advisor(s)

Alexander Greer

Committee Members

Malgorzata Ciszkowska

Jianbo Liu

Subject Categories

Chemistry | Materials Chemistry | Organic Chemistry | Physical Chemistry

Keywords

photodynamic therapy, fluorinated surface, singlet oxygen, drug delivery

Abstract

The thesis describes progress on probe tips for a microoptic device for the precise delivery of the components necessary for photodynamic therapy (PDT) in a highly localized and controllable fashion. The thesis also summarizes results of a photosensitized oxidation study. The work focused on i) developing a photoactive fluoropolymer surface that will release sensitizer drug molecule for use in PDT, ii) designing new probe tips surfaces for use as sensitizer support for a microoptic PDT device, iii) exploring strategies for covalent attachment of sensitizers and model compounds to Teflon/PVA surfaces with the aim of being coupled with our microoptic device, and iv) initiating photosensitized dissociation of peroxides at silica surface by triplet sensitizer energy transfer as a strategy to break peroxide O–O bonds for RO∙ release to study the oxidative process.

Development of a photoactive fluoropolymer surface that releases sensitizer drug molecule was achieved. The surface is a Teflon/poly(vinyl alcohol) (PVA) nanocomposite bearing a photoreleasable PEGylated photosensitizer that generates 1O2 (1Δg) [chlorin e6 methoxy tri(ethylene glycol) trimester]. We observed that the Teflon-like fluorinated surface showed resistance to drug adsorption and that there is also an increase in ground state oxygen by the material. The relative surface efficiency to photorelease the PEGylated sensitizer was slightly higher for the nanocomposite when compared with fluorinated PVG surface. We also found that the presence of C−F bonds in the polymers was beneficial for high O2 solubility, repelling action, and low physical quenching of 1O2. The fluoropolymer could be shaped into device tips to discharge controlled sensitizer and 1O2 quantities for tissue repair or pointsource photodynamic therapy in vivo.

Two different types of probe tips material for a micooptic PDT device were successfully synthesized and their mechanical strength, stability and efficiency for their used as sensitizer support was determined. The surfaces were Teflon-like nanocomposite, made of polyvinyl alcohol (PVA) and polytetrafluoroethylene (PTFE) and a silica monolith, prepared using an acid based catalyzed sol-gel method. Two types of sensitizer-silica monolith surfaces were synthesized: sensitizer coated silica monolith and sensitizer doped silica monolith. Both xerogel surfaces, in presence of light and oxygen, successfully generated singlet oxygen in water which was detected by chemical trapping with alkene, trans-2-methyl-2-pentenoic acid, and anthracene.

PDT sensitizers and model compounds were covalently attached to the plain or succinic acid functionalized Teflon/PVA surface. We were successful in (1) synthesizing 9-bromomethylanthracene-Teflon/PVA heterogeneous surfaces via an alkylation reaction (2) covalently attaching chlorin e6 onto the plain Teflon/PVA surface via bromopropanol linker (3) synthesizing a hybrid Teflon/PVA-9-anthracenemethanol surface by covalently attaching 9-anthracenemethanol via an esterification reaction to the Teflon/PVA surface, previously modified with succinic acid and (4) synthesizing Teflon/PVA probe tip with photo detachable pheophorbide molecules. The heterogeneous surface when placed in solution, in presence of light and oxygen, was observed to show coloration of butanol solution where 99 % sensitizer detached from the probe tip.

Lastly, we explored photochemical reactions at silica surface with the focus on photosensitized dissociation of peroxides. Triplet sensitizer energy transfer as a strategy to break peroxide O–O bonds for RO∙ release was confirmed. We successfully observed the photosensitized dissociation of dicumyl peroxide, upon irradiation of 4,4’-dimethyl benzyl sensitizer adsorbed on fume silica particles. The highest amount of cleaved peroxide (25.3 %) was detected in solution when particles were loaded with dicumyl peroxide: 4,4’-dimethyl benzyl in 1:10 ratio.

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