AMINOPEPTIDASE N RESPONSIVE RESORUFIN-BASED PHOTOTHERANOSTIC AGENT FOR SELECTIVE TREATMENT OF CANCER CELLS

Date

2023-9-5

Author

Sayın, Büşra Asena

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Advancements in cancer therapy continue to evolve, with targeted approaches offering the potential for improved treatment outcomes and reduced side effects. This study explores the utilization of the aminopeptidase N (APN)-responsive resorufin-based photodynamic therapy (PDT) agent, RA-1 for targeted cancer therapy. The investigation includes both the photophysical characterization of RA-1 and its in vitro applications. Photophysical characterization involved analysis of RA-1's reactivity through fluorescence and absorbance measurements. These experiments highlighted the specific activation of RA-1 in response to APN enzymatic activity and time dependent release of the core molecule upon APN exposure. Selectivity of RA-1's activation mechanism was examined through selectivity experiments. These studies established the exquisite selectivity of RA-1's response to APN, further validating its potential as a targeted therapy agent. In vitro photodynamic therapy efficacy of RA-1 was also evaluated. Dark toxicity assessments confirmed the non-toxic nature of RA-1 in the absence of light. PDT treatment experiments demonstrated that RA-1 induced cytotoxicity specifically in APN overexpressing HT1080 cancer cells while maintaining the viability of healthy L929 cells. In order to provide additional evidence about the specificity of RA-1 towards APN in vitro, PDT experiments were performed on the U-87 MG glioblastoma cell line. Despite the well-known cytotoxicity of the iodo-resorufin core in U-87 MG cells, the application of RA-1-based PDT did not exhibit significant cytotoxicity on U-87 MG cell line characterized by low APN expression level. These findings demonstrated the significant selectivity of RA-1 towards APN and indicated the potential of RA-1 on APN-overexpressing cancer cell lines.

Subject Keywords

Photodynamic Therapy, Photosensitizer, Aminopeptidase N, Resorufin

URI

https://hdl.handle.net/11511/105265

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Graduate School of Natural and Applied Sciences, Thesis