Abstract:
Photodynamic therapy (PDT) is a highly promising, clinically approved, and non-invasive treatment modality for several cancer types. A typical PDT action requires, light, tissue oxygen, and a photosensitizer (PS), which are combined to generate cytotoxic singlet oxygen (1O2). Among several challenges in the application of PDT, cancer cell selectivity is the most pronounced and substantial one, which is highly sought to minimize the severe side effects. In this direction activatable photosensitizers (aPS), which tend to stay inactive prior to activation with a tumor associated stimuli, have attracted great interest during last decades. We recently introduced an iodinated resorufin as a red-shifted, water soluble and photostable PS core, which can be also easily converted to an aPS by simply caging the phenolic moiety on the parent structure. To that end, we introduced first ever monoamine oxidase (MAO) activatable PDT agent (R1) based on an iodo-resorufin scaffold. R1 exhibited high 1O2 generation upon activation and induced selective photocytotoxicity towards MAO overexpressing SH-SY5Y neuroblastoma cells. Later, we converted iodo-resorufin core to a hydrogen peroxide (H2O2) responsive PS (RR1) and selectively killed MDA-MB-231 (breast) and HCT-166 (colon) cancer cell upon 595 nm LED irradiation. Additionally, the fluorescence signal of the resorufin core was restored after RR1 reacted with H2O2, suggesting that RR1 can function as a phototheranostic agent. Next, we showed that our parent PS core can be utilized as - galactosidase (β-gal) activatable PS (RB1), when the iodo-resorufin is caged with a sugar moiety. In-vitro cytotoxicity as well as the imaging studies showed that RB-1 induces selective photocytotoxicity towards U87 – glioblastoma cells with high β-gal activity and allows imaging of β-gal-positive cancer cells at the same time. Finally, it is worth to mention all resorufin-based aPSs showed negligible photocytotoxicity towards healthy cells. Our efforts to design new generation PS, which can be activated with different tumor-associated inputs, are in progress.
Biography:
Dr. Kolemen graduated from Chemistry Department at Bilkent University, Turkey in 2008,
where he also got his MSc degree two years later. Dr. Kolemen got his PhD at Bilkent University in 2014, where he trained as an organic chemist under the supervision of Prof. Engin Akkaya. Then, he dived into the field of chemical biology at UC Berkeley, Chemistry Department while working as a postdoctoral scholar in Prof. Christopher Chang’s lab. After joining Koç University, Turkey in 2017, Dr. Kolemen established the “Organic Chemistry and Chemical Biology” lab. In his independent career, he is combining his previous expertise to develop new generation tumor selective phototherapy drugs for cancer treatment and in vivo bio-imaging agents for cancer diagnosis. Dr. Kolemen has recently been awarded with a Science Academy BAGEP 2021 Award, which is given to outstanding young researchers in Turkey.
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