Graduation Year

2025

Document Type

Thesis

Degree

M.S.

Degree Name

Master of Science (M.S.)

Degree Granting Department

Pharmacy

Major Professor

Diane Allen-Gipson, Ph.D.

Committee Member

Qingyu Stephanie Zhou, Ph.D.

Committee Member

Ashwin Parthasarathy, Ph.D.

Committee Member

Vijaykumar Sutariya, Ph.D.

Keywords

Non-small Cell Lung Cancer, Photodynamic Therapy, Folate-Targeted Nanoparticle, Hypoxia, Reactive Oxygen Species

Abstract

Non-small Cell Lung Cancer (NSCLC) is the most common type of lung cancer and is a leading cause of worldwide cancer-related death, which is a strong motivation to develop more efficacious approaches to its treatment. This thesis outlines the construction of folate-targeted bovine serum albumin (FA-BSA) nanoparticles co-loading Chlorin e6 (Ce6), a photodynamic therapy photosensitizer, and Evofosfamide (EVO), a hypoxia-activated prodrug, to enable synergistic photochemotherapy. The 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) is a water-soluble carbodiimide coupling reagent and used for amide bonds between carboxylic acid and amines. FA-BSA nanoparticles were prepared through a desolvation approach and stabilized through crosslinking by the carbodiimide reagent 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) to form spherical particles of narrow size distribution confirmed through dynamic light scattering and transmission electron microscopy. Encapsulation efficiency studies confirmed high drug load of both Ce6 and EVO, giving credence to albumin as a biocompatible carrier molecule. Release studies in vitro indicated sustained and controlled drug release of light-activation-enhanced Ce6-induced reactive oxygen species production and EVO release triggered by light activation that ablated hypoxic tumor environments. Dual-action methodology improved therapeutic potential through folate receptor-mediated endocytic capture of FA-BSA nanoparticles to exploit selective tumor targeting while simultaneously evading tumor resistance and microenvironment obstacles. These results collectively substantiate that FA-BSA tumor-targeting nanocarriers can improve tumor selectivity, enhance retention time, and elevate therapeutic effectiveness while reducing systemic toxicity. This work lays a strong groundwork to explore through translational studies multifunction nanomedicine's translational potential in treating NSCLC.

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