EXPANDING THE SPECTRUM OF PHOTOSENSITIZERS FOR POTENT PHOTODYNAMIC THERAPY AGAINST BRAIN CANCER

Date

2024-5-30

Author

karaman, osman

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Cancer remains one of the foremost global health concern, since effective treatment modalities for a range of cancer types are still elusive. While significant progress has been made in cancer prevention and treatment across various types of cancer, brain tumors persist as an unresolved clinical challenge. Three fundamental issues stand at the forefront of the long-standing challenges of brain cancer treatment: a high percentage of inoperable brain tumors, the limited number of diagnostic and therapeutic drugs can pass through the blood-brain barrier and absence of effective, targeted conventional therapies. Considering the mortality rate, all these challenges in the diagnosis and treatment of brain cancer emphasize the urgent need for alternative, targeted treatment modalities. Photodynamic Therapy (PDT) is an alternative treatment method for diverse cancer types and has attained attention due to minimally invasive nature and fewer side effects compared to current treatment methods. Despite, all these advantages of PDT, limited tissue penetration of light that initiate the activation of photosensitizer hinders the widespread utilization of PDT. To address these challenges, near-infrared (NIR) absorbing, low molecular weighted, brain cancer targeted photosensitizers have emerged. Here, a wide range of advanced fluorophores and photosensitizers with strong Far-Red/NIR absorption, low molecular weight and functionalized with targeting moieties have been developed. Novel synthetic approaches for their synthesis, investigation of their photophysical properties and evaluation of their in vitro efficacy as theranostic PDT agents have been demonstrated. Specifically, photosensitizers based on resorufin and Si-fluorescein exhibited absorption maxima in the red region at 572 nm and 598 nm, respectively. The Si-rhodamine analogue displayed a further red-shifted absorption maximum at 640 nm. Moreover, both resorufin and Si-fluorescein, as well as Si-rhodamine derivatives, demonstrated selectivity towards various brain tumors in in vitro studies. Furthermore, photosensitizers based on phenoselenazine exhibited absorption maxima in the NIR region (>650 nm), and their application in in vitro studies revealed their potential as promising candidates for the treatment of brain cancer.

Subject Keywords

Photodynamic Therapy, Photosensitizer, Brain Cancer, Near Infrared

URI

https://hdl.handle.net/11511/109851

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Graduate School of Natural and Applied Sciences, Thesis