Akademik Veri Yönetim Sistemi
ACS FALL 2023 Harnessing the Power of Data, California, Amerika Birleşik Devletleri, 13 - 17 Ağustos 2023
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-231 which is a highly aggressive,
invasive and poorly differentiated triple-negative breast 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.