UCUNCU RESEARCH GROUP

Research Interests
Ucuncu Research Group
Our research focuses on the functionalization of organic dyes that exhibit fluorescence emission or photosensitization properties through various chemical modifications and their use in theranostic applications. Our studies aim to visualize cancer biomarkers and bacterial infections and to treat them using photodynamic therapy. Additionally, our laboratory conducts research on modifying fluorescent molecules for the analysis of heavy metals, which can be toxic even in trace amounts.
Fluorometric Methods for Disease Detection
The candidate's work in this area can be categorized into two main topics:
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Detection of Cancer Cells
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Detection of Pathogens
1. Detection of Cancer Cells:
Considering global mortality rates, cancer remains the second leading cause of death worldwide. In 2020 alone, 9.9 million people lost their lives due to cancer, accounting for one in every six deaths globally. Many cancer types can be successfully treated if detected at an early stage. However, current cancer screening methods face limitations such as low signal-to-background ratios and restricted accessibility. Our research group aims to address this issue by developing smart molecules that emit fluorescence only in the presence of the target analyte. These highly sensitive, easy-to-use, and relatively inexpensive methods could enable early-stage disease detection.
The candidate's research focuses on detecting biomarkers such as H₂O₂, glutathione, and hypochlorite—found in high concentrations in cancerous regions—in aqueous solutions and cancer models (both in vitro and in vivo). The candidate has completed and ongoing projects on smart molecules capable of both fluorescence emission and electrochemical signal generation.
2. Detection of Pathogens:
Infectious diseases are among the leading causes of global morbidity and mortality. The discovery and development of antibiotics in the early 20th century significantly improved survival rates from bacterial infections, allowing people to live longer and healthier lives. However, the excessive and incorrect use of antibiotics, along with various environmental factors, has led to a global rise in antimicrobial resistance (AMR).
Currently, diagnostic methods for infections require time-consuming protocols, leading to excessive antibiotic use before a definitive diagnosis is made—especially in cases requiring rapid intervention (e.g., intensive care patients). To address this, there is an urgent need for fast and reliable detection methods. The candidate’s work focuses on developing fluorescence-based smart molecules capable of real-time pathogen detection. In both completed and ongoing studies, the candidate is designing new molecules that specifically target and fluoresce in bacterial membranes.
Photodynamic Therapy (PDT)
Our research on PDT can be categorized into two main areas:
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Activatable Photodynamic Therapy
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Antimicrobial Photodynamic Therapy
1. Activatable Photodynamic Therapy:
One of the main challenges in PDT is the low selectivity of reactive oxygen species (ROS). Many photosensitizers, due to their chemical structures, remain continuously active and can generate ROS before reaching the target area upon light exposure. This can cause irreversible damage to healthy cells.
To prevent the production of singlet oxygen and other ROS in non-target cells, researchers have focused on modifying photosensitizers to be quenched and only activated in the presence of a specific biomarker at the target site. The candidate's research focuses on developing approaches where photoactivity-suppressed photosensitizers are activated in cancerous areas with high levels of specific biomarkers (e.g., biothiols) and utilizing bioorthogonal organometallic reactions for two-component activation systems.
2. Antimicrobial Photodynamic Therapy (aPDT):
As previously mentioned, the overuse and misuse of antibiotics have led to a global rise in AMR. Additionally, the challenges of developing new antibiotics and the potential for AMR to emerge rapidly have discouraged pharmaceutical companies from investing in this area. According to a 2016 World Health Organization (WHO) report, the golden age of antibiotics has ended, and without an alternative solution, even minor injuries could become fatal, as they were before the discovery of penicillin.
To combat the rise of AMR and support modern medical practices, it is crucial to develop new diagnostic and therapeutic strategies that do not allow bacteria to develop resistance mechanisms. Antimicrobial photodynamic therapy (aPDT) is a promising approach in this fight, as pathogens cannot develop resistance to singlet oxygen.
Building on knowledge gained from previous studies, the candidate is researching the use of photosensitizers, appropriate wavelengths of light, and molecular oxygen to treat bacterial infections. The candidate's research explores two approaches:
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Modifying antibiotics to eliminate their toxic properties and derivatizing them with photosensitizers for targeted aPDT applications.
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Using low doses of antibiotics, which have not been previously utilized for PDT, to create membrane damage and facilitate the uptake of photosensitizers into bacterial cells.
Additionally, the candidate is working on developing antimicrobial surfaces using electrospun nanofibers for aPDT applications.
Designing Smart Molecules for the Detection of Environmental Pollutants
While technological advancements have provided numerous benefits, they have also significantly contributed to environmental pollution. Pollutants such as heavy metals, which can be released into drinking water and soil through industrial processes, pose a threat to human health and the ecosystem. Heavy metal ions such as Hg²⁺, Cd²⁺, Pb²⁺, Au³⁺, and As³⁺ can cause fatal diseases even in trace amounts.
Traditional analytical methods for detecting heavy metal ions (e.g., atomic absorption/emission spectroscopy, inductively coupled plasma mass spectrometry) have several disadvantages, including complex sample preparation steps and the need for sophisticated instrumentation. In contrast, fluorogenic and chromogenic methods offer several advantages for trace heavy metal detection, such as high analyte sensitivity/selectivity, simple sample preparation, and less complex instrumentation.
One of the candidate's ongoing research areas focuses on developing new fluorescent chemosensors for the selective, sensitive, and rapid detection of environmentally and biologically hazardous heavy metal cations. The candidate’s approach involves modifying fluorophores (such as BODIPY, phenalenone, and NBD) with receptor groups that can react or electrostatically interact with target analytes. Upon interacting with the targeted environmental pollutant, the chemosensor undergoes absorbance/emission changes, which are measured using a spectrophotometer to qualitatively and quantitatively determine the presence of the analyte.