Assoc. Prof. Dr. Bilge GÜVENÇ TUNA
Yeditepe University/Medical Faculty/ Department of Biophysics
Assoc. Prof. Dr. Bilge Güvenç Tuna completed her undergraduate education at Middle East Technical University (METU) Physics Department and her master's degree from Hacettepe University Health Sciences Institute Biophysics Department. She focused on "Smooth muscle biomechanics" at MAYO Clinic in the USA, one of the world's leading investigative medical centers. Assoc. Tuna worked on modeling of blood flow and pressure control, arterial mechanics, smooth muscle plasticity involved in hypertension and vasospasm. After completing her doctoral studies, as a Marie Curie scholar, at the University of Amsterdam Academic Medical Center (AMC), Department of Biomedical Engineering and Physics in 2014, Assoc. Dr. Tuna has been working in Yeditepe University, Faculty of Medicine, Department of Biophysics since 2015.
Dr. Tuna's recent research at Yeditepe University focuses on Aptamers, the development of targeted controlled drug delivery systems, the development of biosensor platforms and disease screening kits, and the role of vascularization and epigenetic modifications in the effect of calorie restriction on aging-related diseases. Dr. Tuna was deemed worthy of the UNESCO L'oreal "For Women in Science" award in 2019, the Science Academy Young Scientists Award Program (BAGEP) in 2021, and the Turkish Academy of Sciences (TÜBA) Outstanding Young Scientist Awards (GEBIP) in 2021.
Application of aptamer conjugated drug delivery systems in cardiovascular diseases
Bilge Guvenc Tuna1, Elif Oztemiz1, Veli Cengiz Ozalp2, Soner Dogan3
1 Department of Biophysics, Faculty of Medicine, Yeditepe University, Istanbul, Turkey
2Department of Medical Biology, Faculty of Medicine, Atilim University, Ankara, Turkey
3Department of Medical Biology, Faculty of Medicine, Yeditepe University, Istanbul, Turkey
E-mail: [email protected]
ABSTRACT
Atherosclerosis, which adversely affects arteries, is a widespread coronary artery disease. In normal cases, the arteries expand and accordingly adjust the amount of blood flow velocity through arteries. Losing flexibility of the arterial wall forms atherosclerotic plaques and these plaques cause clotting of arteries leading to the formation of various complications such as stenosis. At this stage of the disease, it is difficult to reduce plaque formation. Therefore, preventive applications to minimize formation of plaques are considered to be best therapy approach. Statins are commonly used lipid lowering drugs for treatment of hypercholesterolemia and prevention of atherosclerosis. However, high dosages of statins are used to show its effect in clinical practices. Therefore, targeted delivery and controlled release of statins may reduce the concentration needed. Subsequently, this delivery system may minimize the side effects of statins such as adverse muscle events and hepatic dysfunction. Aptamers that have specific affinity against their targets similar to antibodies are single stranded DNA and RNA oligonucleotides. Aptamer sequences can be conjugated to nanoparticles in order to form molecular gates for controlled release of drugs. The aim of this study is to develop an inflammation targeted and controlled release system loaded with atorvastatin. For this purpose, an inflammation-targeted aptamer is used. Intracellular adhesion molecule-1 (ICAM-1), which is known to be increased at atherosclerotic area, is selected for drug delivery target. Aptamer-gated mesoporous silica nanoparticles (MCM-41) loaded with atorvastatin (ATS-NP) were synthesized and characterized by AFM, TEM and BET analysis. Human Umbilical Vein Endothelial Cells (HUVEC) treated with 5nM, 2nM, and 1nM of atorvastatin or equivalent concentration of ATS-NP under low oscillatory flow (LOF) (2 ml/min) or normal laminar flow (NF) (7ml/min) for 24 hour. Then, proteins were isolated and eNOS, peNOS, Akt and pAkt levels were determined by Western Blot analysis. Glyceraldehyde-3-Phosphate Dehydrogenase (GAPDH) used as loading control. Implementation of LOF, mimicking pre-atherosclerotic condition, significantly decreased the eNOS protein expression levels compared to NF. Under LOF conditions 2nM ATS-NP showed the highest eNOS expression compared to other concentrations and the levels were approximately 4 fold higher compared to atorvastatin alone. Parallel with these results, Akt was significantly decreased under LOF. In addition, Akt protein expression was higher in 2nM ATS-NP group than 1nM ATS-NP. As a result, 2nM APT-NP increased eNOS and Akt protein expressions more effectively. In conclusion, synthesizing a targeted and controlled atorvastatin release system can be a viable translational application for the inorganic nano-containers loaded with drugs.
(Supported by L’Oreal-UNESCO Turkey “For woman in science 2019”)