Download Design and Synthesis of ROS-Activatable Fluorescent Probe for Bio

Design and Synthesis of ROS-Activatable
Fluorescent Probe for Bio-Imaging
Master thesis
Department of Chemistry, College of Science,
Korea University at Seoul, 2016
Chang Hoe Kim,
An H2O2-activatable fluorogenic probe, conjugated with indomethacin as a cancerguiding unit, is developed as a potential highly selective and sensitive cancer detection tool.
One of the most important factors to efficiently treat cancer is early stage diagnosis. Currently,
various diagnostic methods have been developed for cancer. Among those, fluorescence
imaging is a promising candidate, because of its high selectivity, sensitivity, and the
possibility of real-time imaging, as well as high spatial resolution. We report a H2O2activatable, COX-2 responsible probe that allows for precise discrimination of cancer from
inflammation with potential applications in cancer treatment. This system is consists of an
H2O2 induced fluorescence signaling unit, and a COX-2 enzyme targeting unit. The COX-2
enzyme is a candidate for selective tumor targeting since it has been found to be
overexpressed in a variety of tumors. Furthermore, COX-2 expression is present at different
levels at tumor sites and inflammatory lesions, but the enzyme rarely expressed in normal
cells. Therefore, this probe allows to distinguish between tumor sites and inflammatory
lesions, as well as normal cells. The probe is highly selective and sensitive for H2O2 and was
found to be stable in aqueous solution of low pH, and various biologically relevant species.
Synthesis and Characterization of BODIPY
Photosensitizers for Suborganelle-targeted
Photodynamic Therapy
Master thesis
Department of Chemistry, College of Science,
Korea University at Seoul, 2016
Yu Jin Jeong,
To improve the anticancer therapeutic efficiency of PDT agents, a series of BODIPY based p
hotosensitizers (BPSs) that can selectively uptake to mitochondria, lysosome and e
ndoplasmic reticulum h a v e b e e n d e s i g n e d and synthesized t o provide different
photocytotoxicity under laser irradiation. This work presents a new insight for achieving
more precise and effective treatment in PDT. And mitochondria targeted photosensitizer (MBPS) is proved to be the most potent PDT agent compare with other members.
Synthesis and Evaluation of
Small molecule based Chemotherapeutics
Master thesis
Department of Chemistry, College of Science,
Korea University at Seoul, 2016
Dong Yeop Lee,
Cancer is the second leading life-threating disease. With the constant increase in
cancer related death globally, there is an urgent need for more efficient drug delivery
framework to meet patient care. Cancer, an irregular cell growth division process, can arise
from any organ or tissue in the body through exogenous agents, altered gene expression, and
protein dysfunctions.In contrast with the normal cell, cancer cell needs much oxygen and
other nutrients for their continuous growth. As a result, new vessels are to be made and
original vessels are degenerated by angiogenesis. The tumor region with less amount of
oxygen concentration is termed as Hypoxia, the condition deprived of adequate oxygen
supply. Solid tumors are characterized as hypoxic tumors due to low, and heterogeneous
concentration of oxygen. Recent reports has cited the presence of overexpressed reductases in
hypoxia cell.
Various chemotherapeutic drugs, including doxorubicin, camptothecin, cisplatin, 5fluorouracil, gemcitabine, and their analogues failed to show notable cytotoxicity and
pharmacokinetics under hypoxic environment. Likewise, and various treatment methods
(Photodynamic therapy and radiation therapy) where oxygen is required as one of the key
reagent to induce toxicity, doesn’t induce desired therapeutic outcomes. In past, numerous
strategies have been adopted including small molecules to nanomedicine, for the
development of hypoxia-activated prodrugs, which demonstrated huge potential for the
hypoxic tumor treatment.
Herein, we have designed and synthesized DOX-NO2-TPP, a hypoxia activated,
cancer cell targeted prodrug system. DOX-NO2-TPP is designed intelligently to prevent the
drug efflux out of the cancer cell, one of the major drawback while cancer treatment with
DOX (doxorubicin). By directing the DOX-NO2-TPP to cancer cell mitochondria, where
drug efflux process is generally less efficient, the Nitro group (hypoxia responsive trigger)
undergoes two electron reduction (hypoxia environment sensitive process) to release the drug
efficiently. We believe that this could be best opportunity for treating multi-drug-resistance
tumors by utilizing hypoxia activation, which has never been highlighted before.