Author

Lalit Chudal

ORCID Identifier(s)

0000-0002-6401-858X

Graduation Semester and Year

2020

Language

English

Document Type

Dissertation

Degree Name

Doctor of Philosophy in Physics and Applied Physics

Department

Physics

First Advisor

Wei Chen

Abstract

This research is focused on using nanotechnology to improve current cancer treatment methods, particularly photodynamic therapy and chemotherapy. Photodynamic therapy, being a local treatment method with low systemic toxicity, has a great deal of potential for cancer treatment. However, due to the lack of oxygen (hypoxia) in the tumor microenvironment and PDT’s intrinsic dependence on oxygen to generate reactive oxygen species, the performance of PDT severely affected in solid tumors. Accordingly, we fabricated a nano-platform that can supply oxygen in cancer cells and subsequently improve the PDT under hypoxic conditions. Protoporphyrin IX, an FDA approved sensitizer, was encapsulated into a liposomal bilayer, and the liposomal surface was coated with MnO2 nanoparticles, which can generate a sufficient level of oxygen by reacting with elevated levels of H2O2 in cancer cells. The nanosystem was well characterized and successfully demonstrated to enhance PDT efficacy by alleviating tumor hypoxia. Another disadvantage of photodynamic therapy is the occurrence of phototoxic effects in PDT treated patients for a prolonged period, particularly if exposed to bright light. This phenomenon can be attributed to the fact that the traditional photosensitizers are easily activatable by visible light. Accordingly, new types of sensitizers that are free of phototoxic effects are desirable. One of the most promising ways to achieve this goal is to develop the sensitizers that are activatable by excitation sources other than visible light. Copper cysteamine nanoparticle that is invented by our group in 2014 meets this criterion as it can be activated by UV light, X-ray, microwave, and ultrasound but not by visible light. Therefore, we anticipate Cu-Cy NPs to have very low phototoxicity due to sunlight irradiation. To validate this hypothesis, a systematic study was conducted to compare the phototoxic effect of Cu-Cy NPs with an FDA approved photosensitizer. The result demonstrated that Cu-Cy NPs caused minimal phototoxic effects when compared to the Protoporphyrin IX, an FDA approved photosensitizer. Current chemotherapeutic drugs lack selectivity, leading to a number of side effects. Fabricating tumor microenvironment responsive drugs is a reliable approach to improve the current chemotherapy for cancer treatment. Due to the existence of Cu1+ on its surface, Cu-Cy NPs may be an excellent heterogeneous Fenton-like catalyst for cancer treatment. Considering the elevated level of H2O2 and low pH conditions, Cu-Cy may produce a significantly higher level of ROS in tumor cell and microenvironment, thereby causing a highly selective cancer-killing effect. Therefore, the third part of this dissertation explores Cu-Cy NPs as a heterogeneous Fenton-like catalyst for highly selective cancer treatment. The result demonstrated that, with IC-50 value of 11 µg/mL (lowest among reported heterogeneous Fenton system) and high selectivity index of 4.5 against cancer cells. Overall, Cu-Cy NPs could be a highly selective chemodynamic drug with low systemic toxicity.

Keywords

Nanoparticles, Cancer

Disciplines

Physical Sciences and Mathematics | Physics

Comments

Degree granted by The University of Texas at Arlington

Included in

Physics Commons

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