Browsing by Author "Sardan, Melis"
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Item Open Access Advances in nanoparticle‐based medical diagnostic and therapeutic techniques(John Wiley & Sons, 2016-03-11) Sardan, Melis; Özkan, Alper Devrim; Zengin, Aygül; Tekinay, Ayşe B.; Güler, Mustafa O.; Güler, Mustafa O.; Tekinay, Ayşe B.Advances in modern medicine have eliminated several major causes of human mortality and considerably extended life expectancies around the world; however, this increase in the global age average has also boosted the incidences of age‐associated disorders. These conditions, such as cancer, neurodegenerative disorders, and cardiovascular disease, severely decrease the quality of life for the affected but are highly polymorphic and often difficult to treat. This chapter describes the characteristics of nanoparticle (NP) contrast agents (CAs) proposed for use in medical imaging, and details the surface modification methods used to designate specific targets for their attachment. It then compares their effectiveness and toxicity compared to conventional methods of contrast enhancement, and discusses the contribution that nanoscience has had, and will have, on medical imaging and disease diagnosis at large.Item Open Access Cell penetrating peptide amphiphile integrated liposomal systems for enhanced delivery of anticancer drugs to tumor cells(Royal Society of Chemistry, 2013) Sardan, Melis; Kilinc, Murat; Genç, Rukan; Tekinay, Ayse B.; Güler, Mustafa O.Liposomes have been extensively used as effective nanocarriers, providing better solubility, higher stability and slower release of drugs compared to free drug administration. They are also preferred due to their nontoxic nature as well as their biodegradability and cell membrane mimicking abilities. In this study, we examined noncovalent integration of a cell penetrating arginine-rich peptide amphiphile into a liposomal formulation of negatively charged 1,2-dioleoyl-sn-glycero-3-[phospho-rac-(1-glycerol)] (DOPG) phospholipids in the presence of cholesterol due to its amphipathic character. We studied changes in the physical characteristics (size, surface potential and membrane polarity) of the liposomal membrane, as well as in the encapsulation of hydrophilic and hydrophobic agents due to peptide amphiphile incorporation. The activities of peptide integrated liposomal systems as drug delivery agents were investigated by using anti-cancer drugs, doxorubicin-HCl and paclitaxel. Enhancement in liposomal uptake due to arginine-rich peptide integration, and enhanced efficacy of the drugs were observed with peptide functionalized liposomes compared to free drugs. © 2013 The Royal Society of Chemistry.Item Open Access Oligonucleotide delivery with cell surface binding and cell penetrating peptide amphiphile nanospheres(American Chemical Society, 2015) Mumcuoğlu, Didem; Sardan, Melis; Tekinay, T.; Güler, Mustafa O.; Tekinay, Ayşe. B.A drug delivery system designed specifically for oligonucleotide therapeutics can ameliorate the problems associated with the in vivo delivery of these molecules. The internalization of free oligonudeotides is challenging, and cytotoxicity is the main obstacle for current transfection vehicles. To develop nontoxic delivery vehicles for efficient transfection of oligonudeotides, we designed a self-assembling peptide amphiphile (PA) nanosphere delivery system decorated with cell penetrating peptides (CPPs) containing multiple arginine residues (R-4 and R-8), and a cell surface binding peptide (KRSR), and report the efficiency of this system in delivering G-3129, a Bcl-2 antisense oligonucleotide (AON). PA/AON (peptide amphiphile/antisense oligonucleotide) complexes were characterized with regards to their size and secondary structure, and their cellular internalization efficiencies were evaluated. The effect of the number of arginine residues on the cellular internalization was investigated by both flow cytometry and confocal imaging, and the results revealed that uptake efficiency improved as the number of arginines in the sequence increased. The combined effect of cell penetration and surface binding property on the cellular internalization and its uptake mechanism was also evaluated by mixing R-8-PA and KRSR-PA. R-8 and R-8/KRSR decorated PAs were found to drastically increase the internalization of AONs compared to nonbioactive PA control. Overall, the KRSR-decorated self-assembled PA nanospheres were demonstrated to be noncytotoxic delivery vectors with high transfection rates and may serve as a promising delivery system for AONs.