Researcher:
Gargari, Ziba Zakeri

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Ziba Zakeri

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Gargari

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Gargari, Ziba Zakeri

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Now showing 1 - 5 of 5
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    Publication
    Mitochondria-loaded alginate-based hydrogel accelerated angiogenesis in a rat model of acute myocardial infarction
    (Elsevier, 2024) Hassanpour, Parisa; Sadeghsoltani, Fatemeh; Haiaty, Sanya; Saghebasl, Solmaz; Izadpanah, Melika; Boroumand, Safieh; Mota, Ali; Rahmati, Mohammad; Rahbarghazi, Reza; Talebi, Mehdi; Rabbani, Shahram; Tafti, Seyed Hossein Ahmadi; Gargari, Ziba Zakeri; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM)
    Here, mitochondria were isolated from mesenchymal stem cells (MSCs) after being treated with mitochondria-stimulating substrates, 50 mu M metformin (Met), and 40 mu M dichloroacetic acid (DCA). The isolated mitochondria (2 x 10(7) particles) were characterized and encapsulated inside 100 mu l hydrogel composed of alginate (3 % w/v; Alg)/gelatin (Gel; 1 % w/v) enriched with 1 mu M pyrrole (Pyr) solidified in the presence of 0.2 M FeCl3. The physicochemical properties and cytocompatibility of prepared hydrogels were assessed using FTIR, swelling, biodegradation, porosity assays, and scanning electron microscopy (SEM). The mitochondria-bearing hydrogel was injected into the ischemic area of rat hearts. FTIR absorption bands represented that the addition of FeCl3 led to polypyrrole (PPy) formation, polysaccharide oxidation, and interaction between Alg and Gel. SEM images exhibited porous structure and the size of pores was reduced in Alg/Gel + PPy group compared to Alg + PPy hydrogel. Based on the data, both Alg + PPy and Alg/Gel + PPy hydrogels can preserve the integrity and morphology of loaded mitochondria. It was noted that Alg/Gel + PPy hydrogel possessed a higher swelling ratio, degradation, and porosity compared to Alg + PPy group. Data confirmed that Alg/Gel + PPy hydrogel containing 1 mu M Pyr yielded the highest survival rate compared to groups with 2 and 4 mu M Pyr (p < 0.05). Injection of mitochondria-loaded Alg/Gel + PPy hydrogel yielded significant restoration of left ventricle thickness compared to the infarction, mitochondria, and Alg/Gel + PPy hydrogel groups 14 days post-injection (p < 0.05). Histological analyses revealed a significant increase of vWF(+) capillaries and alpha-SMA(+) arterioles in the mitochondria-loaded Alg/Gel + PPy hydrogel group (p < 0.05). Immunofluorescence imaging revealed the ability of rat cardiomyocytes to uptake mitochondria alone or after being loaded into Alg/Gel + PPy hydrogel. These effects were evident in the Alg/Gel + PPy group. Taken together, electroconductive Alg-based hydrogels are suitable platforms for the transplantation of cells and organelles and the regeneration of ischemic heart changes.
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    Publication
    Dual targeting salinomycin-loaded smart nanomicelles for enhanced accumulation and therapeutic outcome in breast cancer
    (Elsevier, 2023) Taghipour, Yasamin Davatgaran; Salehi, Roya; Zarebkohan, Amir; Khordadmehr, Monireh; Honar, Yousef Saeedi; Torchilin, Vladimir P.; Gargari, Ziba Zakeri; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM)
    Salinomycin is a polyether compound that exhibits strong anticancer activity and is known as the cancer stem cell inhibitor that reached clinical testing. The rapid elimination of nanoparticles from the bloodstream by the mononuclear phagocyte system (MPS), the liver, and the spleen, accompanied by protein corona (PC) formation, restricts in vivo delivery of nanoparticles in the tumor microenvironment (TME). The DNA aptamer (TA1) that successfully targets the overexpressed CD44 antigen on the surface of breast cancer cells suffers strongly from PC formation in vivo. Thus, cleverly designed targeted strategies that lead to the accumulation of nanoparticles in the tumor become a top priority in the drug delivery field. In this work, dual redox/pH-sensitive poly (& beta;-amino ester) copolymeric micelles modified with CSRLSLPGSSSKpalmSSS peptide and TA1 aptamer, as dual targeting ligands, were synthesized and fully characterized by physico-chemical methods. These biologically transformable stealth NPs were altered into the two ligand-capped (SRL-2 and TA1) NPs for synergistic targeting of the 4T1 breast cancer model after exposure to the TME. The PC formation was reduced sharply in Raw 264.7 cells by increasing the CSRLSLPGSSSKpalmSSS peptide concentration in modified micelles. Surprisingly, in vitro and in vivo biodistribution findings showed that dual targeted micelle accumulation in the TME of 4T1 breast cancer model was significantly higher than that of single modified formulation, along with deep penetration 24 h after intraperitoneal injection. Also, an in vivo treatment study showed remarkable tumor growth inhibition in 4T1 tumorbearing Balb/c mice, compared to different formulations, with a 10% lower therapeutic dose (TD) of SAL that was confirmed by hematoxylin and eosin staining (H & E) and the TUNEL assay. Overall, in this study, we developed smart transformable NPs in which the body's own engineering systems alter their biological identity, which resulted in a reduction in therapeutic dosage along with a lowered off-target effect.
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    Optimization of argon-air DBD plasma-assisted grafting of polyacrylic acid on electrospun POSS-PCUU
    (Pergamon-Elsevier Science Ltd, 2023) Salehi, Roya; Mahkam, Mehrdad; Siahpoush, Vahid; Rahbarghazi, Reza; l; Abbasi, Farhang; Gargari, Ziba Zakeri; Sokullu, Emel; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine
    It is accepted that significant interfacial reactions take place in engineered tissues between biomaterial surfaces and the host's tissue in the body. The lack of appropriate functional groups limits long-term biocompatibility and successful biological response of biomaterials. Therefore, the cell-biomaterial affinity should be increased by functional groups grafting to the surface of biomaterials which provide the basic properties of the desired tissue. For the first time in this study, PAAc grafting was performed using two-step argon-air DBD plasma at atmospheric pressure in a few seconds of exposure time, to modify the surface of POSS-PCUU nanofibers to selectively in-crease their superficial properties while maintaining the required mechanical properties. The Response Surface Methodology was used for experimental design to optimize the operating conditions of carboxylic acid grafting at the electrospun POSS-PCUU surface. Nanofiber surface modification was confirmed using ATR-FTIR, FE-SEM, AFM, WCA, and tensile test. The grafting of PAAc to the nanofiber surface was proved by the presence of a broad hydroxyl band in ATR-FTIR spectrum, the morphological changes observed in the SEM and AFM images, and the reduction of the water contact angle. The stress-strain behavior at the optimum point also showed an acceptable reduction in tensile strength. Furthermore, the effects of two variables, plasma processing time and plasma copolymerization time were optimized and investigated using the CCD method at five levels of carboxylic acid grafting density. The grafting of PAAc onto the nanofiber surface (73.69 +/- 2.1 mu g/cm2) produced at reaction conditions displayed great agreement with the predicted results by the model. Results showed that the modified PAAc-POSS-PCUU nanofibers will be a desirable surface for the immobilization of various ECM proteins with high potential in small-diameter vascular graft applications.
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    Publication
    Robust adhesive nanocomposite sponge composed of citric acid and nano clays modified cellulose for rapid hemostasis of lethal non-compressible hemorrhage
    (Elsevier Ltd, 2024) Mahmoodzadeh,A; Valizadeh,N; Edalati,M; Khordadmehr,M; Salehi,R; Jarolmasjed,S; Gargari, Ziba Zakeri; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM)
    Massive bleeding control plays the main role in saving people's lives in emergency situations. Herein, modified cellulose-based nanocomposite sponges by polydopamine (PDA) and laponite nano-clay was developed to sturdily deal with non-compressible lethal severe bleeding. PDA accomplishes supreme adhesion in the bleeding site (similar to 405 kPa) to form strong physical barrier and seal the position. Sponges super porous (similar to 70 % porosity) and super absorbent capacity (48 g blood absorbed per 1 g sponge) by concentrating the blood cells and platelets provides the requirements for primary hemostasis. Synergistically, the nanocomposite sponges' intelligent chemical structure induces hemostasis by activation of the XI, IX, X, II and FVII factors of intrinsic and extrinsic coagulation pathways. Excellent hemostatic performance of sponges in-vitro was assessed by RBC accumulation (similar to 100 %), blood clotting index (similar to 10 %), platelet aggregation/activation (-93 %) and clotting time. The nanocomposite sponges depicted super performance in the fatal high-pressure non-compressible hemorrhage model by reducing of >2, 15 and 3 times in the bleeding amount at New Zealand rabbit's heart and liver, and rat's femoral artery bleeding models, respectively compared to commercial hemostatic agents (Pvalue<0.001). The in-vivo host response results exhibited biosafety with no systemic and significant local inflammatory response by hematological, pathological and biochemical parameters assessments.
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    Exosomes encapsulated in hydrogels for effective central nervous system drug delivery
    (Royal Soc Chemistry, 2024) Kocaarslan, Azra; Saghati, Sepideh; Yağcı, Yusuf; Rahbarghazi, Reza; Department of Mechanical Engineering; Department of Mechanical Engineering; Gargari, Ziba Zakeri; Metin, Ecem; Hosseinikarimi, Nasır Seyed; Vural, Atay; Akyoldaş, Göktuğ; Baysal, Kemal; Özdemir, Yasemin Gürsoy; Taşoğlu, Savaş; Sokullu, Emel; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Graduate School of Health Sciences; College of Sciences; School of Medicine; College of Engineering
    The targeted delivery of pharmacologically active molecules, metabolites, and growth factors to the brain parenchyma has become one of the major challenges following the onset of neurodegeneration and pathological conditions. The therapeutic effect of active biomolecules is significantly impaired after systemic administration in the central nervous system (CNS) because of the blood-brain barrier (BBB). Therefore, the development of novel therapeutic approaches capable of overcoming these limitations is under discussion. Exosomes (Exo) are nano-sized vesicles of endosomal origin that have a high distribution rate in biofluids. Recent advances have introduced Exo as naturally suitable bio-shuttles for the delivery of neurotrophic factors to the brain parenchyma. In recent years, many researchers have attempted to regulate the delivery of Exo to target sites while reducing their removal from circulation. The encapsulation of Exo in natural and synthetic hydrogels offers a valuable strategy to address the limitations of Exo, maintaining their integrity and controlling their release at a desired site. Herein, we highlight the current and novel approaches related to the application of hydrogels for the encapsulation of Exo in the field of CNS tissue engineering. The targeted delivery of pharmacologically active molecules, metabolites, and growth factors to the brain parenchyma has become one of the major challenges following the onset of neurodegeneration and pathological conditions.