NIR ABSORBING PHENOSELENAZINE BASED PDT AGENTS TOWARDS EFFECTIVE TREATMENT OF TRIPLE NEGATIVE BREAST CANCER

Date

2023-08-16

Author

Karaman, Osman
Günbaş, Emrullah Görkem

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Cancer is still one of the leading health issues globally since effective treatment modalities for a range of cancer types are still elusive. Even with immense efforts in cancer research for diagnosis and treatment, vast number of people are diagnosed with cancer each year and unfortunately increase in survival rates in average are not meeting expectations. At this point alternative treatment modalities such as photodynamic therapy (PDT) has attained attention due to minimally invasive nature and fewer side effects compared to current treatment methods. Ease of operation, tumor selectivity, lower cost and compatibility to diverse tumor types via modifiable active sites of photosensitizers makes PDT effective alternative for cancer therapy. In PDT, patient administrated with photosensitizer (PS) and irradiated with light which triggers the generation of reactive oxygen species (ROS) preferably singlet oxygen (1O2) which end up with cell death. Activation of PS in tumor region with excitation light and short lifetime of singlet oxygen in aqueous medium provide selective treatment while leaving healthy cells unaffected. Beside all these advantageous of PDT, limited tissue penetration ability of light, which activates PS, hinders the widespread usage of therapy.In this work, NIR absorbing, cancer selective phenoselenazine based photosensitizer, NSeMorph was synthesized and its photophysical properties were investigated. NSeMorph has absorption maximum in therapeutic window as expected (λabs = 671 nm, λem = 701 nm) which enable its utilization in deeper tissues. High singlet oxygen quantum yield in aqueous medium ( FΔ =73% with respect to methylene blue) reveals its potential as a strong PDT agent. Relatively small molecular weight, compact structure and controlled lipophilicity of PS makes it a potent candidate for brain cancer treatment. Also, in vitro studies promote the photophysical properties of NSeMorph. First, was tested in peripheral cell lines.Along with low IC50 values in diverse cancer cell lines (MDA-MB 231 = 1.17 μM, MCF-7 = 0.57 μM, upon 1 h irradiation, HeLa cells = 1.91 μM upon 0.5 h irradiation) especially in MDA-MB-231which is a highly aggressive, invasive and poorly differentiatedtriple-negativebreast cancer neither significant dark toxicity nor toxicity toward healthy cells upon irradiation ( L929 = 20 μM< ) were observed and lead us to test in central cell lines. For this purpose, Nitroreductase (NTR) selective cage group was introduced to NSeMorph to increase cancer selectivity and cell culture studies still ongoing. All in all, promising PDT agent NSeMorph and NTR caged NSeMorph were synthesized, photophysical properties of NSeMorph were investigated and in vitro studies were performed. NTR caged NSeMorph will be tested in both peripheral and central cell lines. The complete results will be presented.

URI

https://hdl.handle.net/11511/107172

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Department of Chemistry, Conference / Seminar