Browsing by Author "Hamsici, S."

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Open Access
Bioactive peptide functionalized aligned cyclodextrin nanofibers for neurite outgrowth
(Royal Society of Chemistry, 2017) Hamsici, S.; Cinar, G.; Celebioglu A.; Uyar, Tamer; Tekinay, A. B.; Güler, Mustafa O.
Guidance of neurite extension and establishment of neural connectivity hold great importance for neural tissue regeneration and neural conduit implants. Although bioactive-epitope functionalized synthetic or natural polymeric materials have been proposed for the induction of neural regeneration, chemical modifications of these materials for neural differentiation still remain a challenge due to the harsh conditions of chemical reactions, along with non-homogeneous surface modifications. In this study, a facile noncovalent functionalization method is proposed by exploiting host-guest interactions between an adamantane-conjugated laminin derived bioactive IKVAV epitope and electrospun cyclodextrin nanofibers (CDNFs) to fabricate implantable scaffolds for peripheral nerve regeneration. While electrospun CDNFs introduce a three-dimensional biocompatible microenvironment to promote cellular viability and adhesion, the bioactive epitopes presented on the surface of electrospun CDNFs guide the cellular differentiation of PC-12 cells. In addition to materials synthesis and smart functionalization, physical alignment of the electrospun nanofibers guides the cells for enhanced differentiation. Cells cultured on aligned and IKVAV functionalized electrospun CDNFs had significantly higher expression of neuron-specific βIII-tubulin and synaptophysin. The neurite extension is also higher on the bioactive aligned scaffolds compared to random and non-functionalized electrospun CDNFs. Both chemical and physical cues were utilized for an effective neuronal differentiation process. © The Royal Society of Chemistry.
Open Access
Gemcitabine integrated nano-prodrug carrier system
(American Chemical Society, 2017) Hamsici, S.; Ekiz, M. S.; Ciftci, G. C.; Tekinay, A. B.; Güler, Mustafa O.
Peptide nanomaterials have received a great deal of interest in drug-delivery applications due to their biodegradability, biocompatibility, suitability for large-scale synthesis, high drug-loading capacities, targeting ability, and ordered structural organization. The covalent conjugation of drugs to peptide backbones results in prolonged circulation time and improved stability of drugs. Therapeutic efficacy of gemcitabine, which is used for breast cancer treatment, is severely compromised due to its rapid plasma degradation. Its hydrophilic nature poses a challenge for both its efficient encapsulation into nanocarrier systems and its sustained release property. Here, we designed a new peptide prodrug molecule for the anticancer drug gemcitabine, which was covalently conjugated to the C-terminal of 9-fluorenylmethoxy carbonyl (Fmoc)-protected glycine. The prodrug was further integrated into peptide nanocarrier system through noncovalent interactions. A pair of oppositely charged amyloid-inspired peptides (Fmoc-AIPs) were exploited as components of the drug-carrier system and self-assembled into one-dimensional nanofibers at physiological conditions. The gemcitabine integrated nanoprodrug carrier system exhibited slow release and reduced the cellular viability of 4T1 breast cancer cell line in a time- and concentration-dependent manner.
Open Access
Local delivery of doxorubicin through supramolecular peptide amphiphile nanofiber gels
(Royal Society of Chemistry, 2017) Cinar, G.; Ozdemir, A.; Hamsici, S.; Gunay, G.; Dana, A.; Tekinay, A. B.; Güler, Mustafa O.
Peptide amphiphiles (PAs) self-assemble into supramolecular nanofiber gels that provide a suitable environment for encapsulation of both hydrophobic and hydrophilic molecules. The PA gels have significant advantages for controlled delivery applications due to their high capacity to retain water, biocompatibility, and biodegradability. In this study, we demonstrate injectable supramolecular PA nanofiber gels for drug delivery applications. Doxorubicin (Dox), as a widely used chemotherapeutic drug for breast cancer treatment, was encapsulated within the PA gels prepared at different concentrations. Physical and chemical properties of the gels were characterized, and slow release of the Dox molecules through the supramolecular PA nanofiber gels was studied. In addition, the diffusion constants of the drug molecules within the PA nanofiber gels were estimated using fluorescence recovery after the photobleaching (FRAP) method. The PA nanofiber gels did not show any cytotoxicity and the encapsulation strategy enhanced the activity of drug molecules on cellular viability through prolonged release compared to direct administration under in vitro conditions. Moreover, the local in vivo injection of the Dox encapsulated PA nanofiber gels (Dox/PA) to the tumor site demonstrated the lowest tumor growth rate compared to the direct Dox injection and increased the apoptotic cells within the tumor tissue for local drug release through the PA nanofiber gels under in vivo conditions.