Browsing by Subject "Peptide drugs."

Now showing 1 - 3 of 3

Open Access
Cell penetrating peptide amphiphile integrated liposomal systems for enhanced delivery of cargo to tumor cells
(2013) Kılınç, Murat
Liposomes have been extensively utilized as effective nanocarriers due to their enhanced solubility, higher stability and greater ability to facilitate the slow release of encapsulated drugs compared to free drug administrations. Liposomes are also preferred as drug vectors due to their non-toxic nature, biodegradability and structural resemblance to the cell membrane. However, their low internalization efficiencies pose an important challenge for their use in drug delivery applications. Internalization issues inherent in many liposomal systems can be circumvented by the use of cell penetrating peptides, which non-covalently attach on the liposome surface and greatly enhance liposomal uptake in a receptor- and charge-dependent manner. In this study, we examined the liposomal dynamics effected through the integration of an amphiphilic cell penetrating peptide into a simple liposome system. Peptide amphiphiles with a cell penetrating arginine-rich domain were incorporated into liposomal membranes formed by negatively charged dioleoylphosphoglycerol (DOPG) phospholipids in the presence of cholesterol. Throughout the present study, we sought to analyze the effect of peptide incorporation on (a) the physical characteristics, such as size, surface potential and membrane polarity, of the liposomal membrane, (b) the alterations in the encapsulation and delivery mechanisms of hydrophilic (Rhodamine B) and hydrophobic (Nile Red) drug models and (c) the enhancement of therapeutic capability in liposomes loaded with the drugs Doxorubicin-HCl and Paclitaxel. Our results revealed that the modification of liposomes by cell penetrating peptide amphiphiles results in the improvement of cargo delivery and the enhancement of the therapeutic effects of the anticancer drugs Doxurubicin and Paclitaxel.
Open Access
Identification and the characterization of small molecules with potential anticancer activity against solid tumors
(2011) Durmaz, İrem
The ultimate goal of our project was to investigate candiate small molecules with a potential anticancer activity and characterize their mode of action. Cardiac glycosides are important group of molecules for both their treating properties in heart failure and their potential effects in cancer therapy. We investigated the cardiac glycosides that are extracted from Digitalis Ferruginea which can be frequently found in Turkey. These glycosides are Lanatoside A, Lanatoside C and Glucogitorosid. Our results showed that they constitute high cytotoxicity effect against liver cancer cell lines. In addition they cause G2/M cell cycle arrest and thereby induce apoptosis. For the synthetic molecules, we first tested a set of molecules that are synthesized as derivatives of kinase inhibitors. There are some commercial drugs such as imatinib or erlotinib that are used frequently for cancer treatment. Thus we wanted to investigate if these molecules comprise cytotoxic activities. Our data revealed that especially one of the molecules out of 16 display high cytotoxicity and high kinase inhibitory effect in liver cancer cell lines. The final group of molecules we tested was compoused of thiazolidine ring. In this group of molecules, only one molecule, the one with alkyne terminal precursor, caused cytotoxicity against cancer cell lines. Besides, we have shown that it induces SubG1/G1 cell cycle arrest in cancer cell lines.
Unknown
Slow release and delivery of antisense oligonucleotide drug by self-assembled peptide amphiphile nanofibers
(2012) Bulut, Selma
Antisense oligonucleotides are short single stranded DNA sequences and they are suggested to be used for treatment of several disorders including cancer. They could enter the cell and specifically inhibit the target gene, however chemical stability, controlled release and intracellular delivery are areas that has to be focused on to increase their efficacy. Gels composed of nanofibrous peptide network have been previously suggested as carriers for controlled delivery of drugs to improve stability and to provide controlled release, but have not been used for oligonucleotide delivery. In this work, a self-assembled peptide nanofibrous system is formed by mixing a cationic peptide amphiphile (PA) with Bcl-2 antisense oligodeoxynucleotide (ODN), G3139, through electrostatic interactions. The self-assembly of PA-ODN gel was characterized by circular dichroism, rheology, atomic force microscopy (AFM) and scanning electron microscopy (SEM). AFM and SEM images revealed establishment of the nanofibrous PA-ODN network. Due to the electrostatic interactions between PA and ODN, ODN release can be controlled by changing PA and ODN concentrations in the PA-ODN gel. Cellular delivery of the ODN by PA-ODN nanofiber complex was observed by fluorescently labeled ODN molecule. Cells incubated with PA-ODN complex had enhanced cellular uptake compared to cells incubated with naked ODN. Furthermore, Bcl-2 mRNA amounts were lower in MCF-7 human breast cancer cells in the presence of PA-ODN complex compared to naked ODN and mismatch ODN evidenced by quantitative RT-PCR studies. These results suggest that PA molecules can control ODN release, enhance cellular uptake and present a novel efficient approach for gene therapy studies and oligonucleotide based drug delivery. In follow-up studies, increase in the internalization efficacy of ODN by incorporation of bioactive sequences, RGDS, to peptide sequence was also shown.