Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7148
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Article Citation - WoS: 6Citation - Scopus: 7A Comprehensive Study on Doxorubicin-Loaded Aspartic Acid-Coated Magnetic Fe<sub>3</Sub>o<sub>4< Nanoparticles: Synthesis, Characterization and in Vitro Anticancer Investigations(Elsevier, 2024) Jafari, Nahideh; Mohammadpourfard, Mousa; Hamishehkar, HamedMagnetic Fe3O4 nanoparticles (MNPs) hold significant potential across various scientific fields due to their notable properties. For biomedical applications, MNPs must be biocompatible, stable, and possess high magnetic potential. Aspartic acid (ASP) as a coating agent not only provides biocompatibility, stability, and high magnetic potential but also offers the potential for absorbing various drugs for targeted delivery due to its carboxyl and amino functional groups. So, in this study, we synthesized ASP-coated MNPs (ASP-MNPs) through a one-step co-precipitation method and loaded doxorubicin (DOX) onto these nanoparticles to create DOX-ASP-MNPs for targeted drug delivery. Characterization of the nanoparticle confirmed the crystal structure, spherical morphology, and improved size distribution of ASP-MNPs (8.53 +/- 2.56 nm) compared to uncoated MNPs (7.05 +/- 1.89 nm), as analyzed by XRD, FESEM, and TEM. FT-IR and zeta potential assessments (ZP = -6.3 mV for MNPs, ZP = -31.1 mV for ASP-MNPs) verified successful ASP binding, DOX loading, and nanoparticle stability. VSM analysis indicated a slight decrease in saturation magnetism after coating (51.1 emu/g) compared to MNPs (57.4 emu/g). In vitro release studies demonstrated a higher release rate (83 %) of DOX-ASP-MNPs at pH 5.2, indicating their suitability for cancerous cells. Cytotoxicity assays on A-549 cancer cell lines showed a dose-dependent response. DAPI staining revealed that free DOX caused more DNA damage. Cellular uptake studies indicated a time-dependent uptake of DOX-ASP-MNPs, higher at 3 h compared to 1 h, though lower than free DOX uptake due to different uptake pathways. Apoptosis assays over 72 h showed similar apoptotic rates for DOX-ASP-MNPs and free DOX. These findings suggest that ASP-MNPs possess enhanced physicochemical properties and effective drug delivery capabilities, making them a promising candidate for different biomedical applications, particularly targeted cancer therapy.Review Citation - WoS: 9Citation - Scopus: 7Micrornas and Long Non-Coding Rnas as Novel Targets in Anti-Cancer Drug Development(Bentham Science Publishers, 2023) Çetinkaya, Melisa; Baran, YusufNon-coding RNAs comprise the majority of RNAs that have been transcribed from the human genome, and these non-coding RNAs have essential regulatory roles in the cellular processes. They have been discovered to influence the expression of the genes, including tumor-suppressive and oncogenes, that establish the non-coding RNAs as novel targets for anti-cancer drug development. Among non-coding RNAs, microRNAs have been extensively studied in terms of cancer biology, and some microRNA-based therapeutics have been reached in clinical studies. Even though most of the research regarding targeting non-coding RNAs for anti-cancer drug development focused on microRNAs, long non-coding RNAs have also started to gain importance as potential therapeutic targets for cancer therapy. In this chapter, the strategies and importance of targeting microRNAs and long non-coding RNAs will be described, along with the clinical studies that involve microRNA-based cancer therapeutics and preclinical studies that involve long non-coding RNA-based therapeutics. Finally, the delivery strategies that have great importance in the effective delivery of the non-coding RNA-based cancer therapeutics, hence the therapy's effectiveness, will be described.Article Citation - WoS: 10Citation - Scopus: 10An in Vivo Zebrafish Model Reveals Circulating Tumor Cell Targeting Capacity of Serum Albumin Nanoparticles(Elsevier, 2022) Çakan Akdoğan, Gülçin; Ersöz, Esra; Sözer, Sümeyra Çiğdem; Gelinci, EmineNanoparticles are promising tools of drug delivery in modern medicine. There is a need for fast and reliable models for in vivo validation of newly developed nanocarriers. Here, we report a fast and easy zebrafish larval model to study the biodistribution and cancer cell targeting capacity of serum albumin nanoparticles in vivo. Fluorescently tagged Bovine Serum Albumin Nanoparticles (BSA-NPs) delivered intravenously to the zebrafish larvae, can be used to study the biodistribution via live imaging. We showed that the BSA-NPs were instantly distributed to the larval vasculature including the brain, without causing any toxicity. The clearance of nanoparticles from the body occurred within few days, which gives sufficient time to study anti-cancer efficiency of the BSA-NPs. Next, we asked whether the BSA-NPs can target the cancer cells in circulation. We established a circulating tumor cell (CTC) xenograft model and described a quantitative method for colocalization and cancer cell death analysis in the intact live organism. We showed that BSA-NPs effectively found and localized to MCF7 cells in vasculature which were killed upon doxorubicin delivery. Interestingly, folic acid coating of BSA-NPs caused faster colocalization but did not increase the overall cell death. This is the first report of the biodistribution, toxicity and anti-cancer effectiveness of serum albumin-based nanoparticles in the zebrafish model. Moreover, here we report for the first time that BSA-NPs are able to target the CTCs in an in vivo model. The zebrafish CTC model and the analysis protocol reported here can be used to assess CTC targeting capacity of nanoparticles and devise patient specific CTC targeting tests.Article Citation - WoS: 11Citation - Scopus: 12Expandable Polymer Assisted Wearable Personalized Medicinal Platform(Wiley, 2020) Babatain, Wedyan; Wicaksono, Irmandy; Buttner, Ulrich; El-atab, Nazek; Rehman, Mutee Ur; Hussain, Muhammad Mustafa; Gümüş, AbdurrahmanConventional healthcare, thoughts of treatment, and practice of medicine largely rely on the traditional concept of one size fits all. Personalized medicine is an emerging therapeutic approach that aims to develop a therapeutic technique that provides tailor-made therapy based on everyone's individual needs by delivering the right drug at the right time with the right amount of dosage. Advancement in technologies such as wearable biosensors, point-of-care diagnostics, microfluidics, and artificial intelligence can enable the realization of effective personalized therapy. However, currently, there is a lack of a personalized minimally invasive wearable closed-loop drug delivery system that is continuous, automated, conformal to the skin, and cost-effective. Here, design, fabrication, optimization, and application of a personalized medicinal platform augmented with flexible biosensors, heaters, expandable actuator and processing units powered by a lightweight battery are shown. The platform provides precise drug delivery and preparation with spatiotemporal control over the administered dose as a response to real-time physiological changes of the individual. The system is conformal to the skin, and the drug is transdermally administered through an integrated microneedle. The developed platform is fabricated using rapid, cost-effective techniques that are independent of advanced microfabrication facilities to expand its applications to low-resource environments.Article Citation - WoS: 27Citation - Scopus: 34Chitosan/Montmorillonite Composite Nanospheres for Sustained Antibiotic Delivery at Post-Implantation Bone Infection Treatment(IOP Publishing Ltd., 2019) Kımna, Ceren; Değer, Sibel; Tamburacı, Sedef; Tıhmınlıoğlu, FundaDespite the advancements in bone transplantation operations, inflammation is still a serious problem that threatens human health at the post-implantation period. Conventional antibiotic therapy methods may lead to some side effects such as ototoxicity and nephrotoxicity, especially when applied in high doses. Therefore, local drug delivery systems play a vital role in bone disorders due to the elimination of the disadvantages introduced by conventional methods. In the presented study, it was aimed to develop Vancomycin (VC) and Gentamicin (GC) loaded chitosan-montmorillonite nanoclay composites (CS/MMT) to provide required antibiotic doses to combat post-implantation infection. CS/MMT nanocomposite formation was supplied by microfluidizer homogenization and spherical drug carrier nanoparticles were obtained by electrospraying technique. Three factors; voltage, distance and flowrate were varied to fabricate spherical nanoparticles with uniform size. Emprical model was developed to predict nanosphere size by altering process variables. Nanospheres were characterized in terms of morphology, hydrodynamic size, zeta potential, drug encapsulation efficiency and release profile. Drug loaded nanospheres have been successfully produced with a size range of 180-350 nm. Nanocomposite drug carriers showed high encapsulation efficiency (80%-95%) and prolonged release period when compared to bare chitosan nanospheres. The drug release from nanocomposite carriers was monitored by diffusion mechanism up to 30 d. The in vitro release medium of nanospheres showed strong antimicrobial activity against gram-positive S. aureus and gram-negative E. coli bacteria. Furthermore, it was found that the nanospheres did not show any cytotoxic effect to fibroblast (NIH/3T3) and osteoblast (SaOS-2) cell lines. The results demonstrated that the prepared composite nanospheres can be a promising option for bone infection prevention at the post implantation period.Article Citation - WoS: 59Citation - Scopus: 57Cmos Enabled Microfluidic Systems for Healthcare Based Applications(John Wiley and Sons Inc., 2018) Hussian, Muhammad M.; Khan, Sherjeel M.; Gümüş, Abdurrahman; Nassar, Joanna M.With the increased global population, it is more important than ever to expand accessibility to affordable personalized healthcare. In this context, a seamless integration of microfluidic technology for bioanalysis and drug delivery and complementary metal oxide semiconductor (CMOS) technology enabled data-management circuitry is critical. Therefore, here, the fundamentals, integration aspects, and applications of CMOS-enabled microfluidic systems for affordable personalized healthcare systems are presented. Critical components, like sensors, actuators, and their fabrication and packaging, are discussed and reviewed in detail. With the emergence of the Internet-of-Things and the upcoming Internet-of-Everything for a people–process–data–device connected world, now is the time to take CMOS-enabled microfluidics technology to as many people as possible. There is enormous potential for microfluidic technologies in affordable healthcare for everyone, and CMOS technology will play a major role in making that happen.Book Part Citation - WoS: 30Citation - Scopus: 41Nanocarriers for Plant-Derived Natural Compounds(Elsevier Ltd., 2017) Bayraktar, Oğuz; Erdoğan, İpek; Köse, Merve D.; Kalmaz, GülcanNatural products constitute a large fraction in drug discovery processes. The term includes compounds from plants, microorganisms, and animals. Most of the natural products are secondary metabolites derived from plants, which are low in amounts and difficult to isolate. Another issue is the preservation of their bioactivity during process and storage as well as degradation in the gastrointestinal system before reaching circulation. Advances in nanotechnology offer nanoparticles, nanocapsules, and conjugates, which are devoted to site-specific, time-controlled delivery of bioactive agents. Nanoencapsulated systems have the advantage of high drug encapsulation efficiency because of optimized drug solubility in the core, low polymer content compared to other nanoparticulated systems such as nanospheres, drug polymeric shell protection against degradation factors, and the reduction of tissue irritation caused by the polymeric shell. This chapter will discuss nanoencapsulation methods and advances in carrier systems for plant-derived natural compounds.Article Citation - WoS: 39Citation - Scopus: 37Enhancing Tumor Cell Response To Multidrug Resistance With Ph-Sensitive Quercetin and Doxorubicin Conjugated Multifunctional Nanoparticles(Elsevier Ltd., 2017) Dağlıoğlu, CenkClassical chemotherapy uses chemotherapeutic agents as a mainstay of anticancer treatment. However, the development of multidrug resistance to chemotherapy limits the effectiveness of current cancer treatment. Nanosized bioconjugates combining a chemotherapeutic agent with a pharmacological approach may improve the curative effect of chemotherapeutic agents. Herein I addressed this issue by describing the synthesis, and testing of, pH-responsive Fe3O4@SiO2(FITC)-BTN/QUR/DOX multifunctional nanoparticles. The particles were designed to modulate resistance-mediating factors and to potentiate the efficacy of DOX against chemoresistance. The physicochemical properties of the nanoparticles were characterized based on the combination of several techniques: dynamic light scattering (DLS), zeta-potential measurement, Fourier transform infrared spectroscopy (FTIR), electron microscopy techniques (SEM and STEM with EDX) and an in vitro pH-dependent release study. Cellular uptake and cytotoxicity experiments demonstrated enhanced intracellular delivery and retention of nanoparticles in the cytoplasm and efficient reduction of cancer cell viability in drug-resistant lung carcinoma A549/DOX cell lines. This did not affect internalization and viability of an immortalized human lung epithelial cell line BEAS-2B. Moreover, proapoptotic and antiproliferative studies showed that Fe3O4@SiO2(FITC)-BTN/QUR/DOX nanoparticles can promote apoptosis, inhibit tumor cell proliferation, and enhance the chemotherapeutic effects of DOX against multidrug resistance. These results confirm that this multifunctional platform possesses significant synergy between QUR and DOX and is promising for development as an antitumor treatment in cancer therapy.Article Citation - WoS: 33Citation - Scopus: 36Epr Studies of Intermolecular Interactions and Competitive Binding of Drugs in a Drug-Bsa Binding Model(Royal Society of Chemistry, 2016) Akdoğan, Yaşar; Emrullahoğlu, Mustafa; Tatlıdil, Diğdem; Üçüncü, Muhammed; Çakan Akdoğan, GülçinUnderstanding intermolecular interactions between drugs and proteins is very important in drug delivery studies. Here, we studied different binding interactions between salicylic acid and bovine serum albumin (BSA) using electron paramagnetic resonance (EPR) spectroscopy. Salicylic acid was labeled with a stable radical (spin label) in order to monitor its mobilized (free) or immobilized (bound to BSA) states. In addition to spin labeled salicylic acid (SL-salicylic acid), its derivatives including SL-benzoic acid, SL-phenol, SL-benzene, SL-cyclohexane and SL-hexane were synthesized to reveal the effects of various drug binding interactions. EPR results of these SL-molecules showed that hydrophobic interaction is the main driving force. Whereas each of the two functional groups (-COOH and -OH) on the benzene ring has a minute but detectable effect on the drug-protein complex formation. In order to investigate the effect of electrostatic interaction on drug binding, cationic BSA (cBSA) was synthesized, altering the negative net charge of BSA to positive. The salicylic acid loading capacity of cBSA is significantly higher compared to that of BSA, indicating the importance of electrostatic interaction in drug binding. Moreover, the competitive binding properties of salicylic acid, ibuprofen and aspirin to BSA were studied. The combined EPR results of SL-salicylic acid/ibuprofen and SL-ibuprofen/salicylic acid showed that ibuprofen is able to replace up to ∼83% of bound SL-salicylic acid, and salicylic acid can replace only ∼14% of the bound SL-ibuprofen. This indicates that ∼97% of all salicylic acid and ibuprofen binding sites are shared. On the other hand, aspirin replaces only ∼23% of bound SL-salicylic acid, and salicylic acid replaces ∼50% of bound SL-aspirin, indicating that ∼73% of all salicylic acid and aspirin binding sites are shared. These results show that EPR spectroscopy in combination with the spin labeling technique is a very powerful method to investigate drug binding dynamics in detail.Article Citation - WoS: 17Citation - Scopus: 16Ph-Labile Sheddable Block Copolymers by Raft Polymerization: Synthesis and Potential Use as Sirna Conjugates(Elsevier Ltd., 2013) Huang, Xin; Sevimli, Sema İlknur; Bulmuş, VolgaWell-defined amphiphilic block copolymers composed of hydrophilic and hydrophobic blocks linked through an acid-labile acetal bond were synthesized directly by RAFT polymerization using a new poly(ethylene glycol) (PEG) macroRAFT agent modified with an acid-labile group at its R-terminal. The new macroRAFT agent was used for polymerization of poly(t-butyl methacrylate) (PtBMA) or poly(cholesterol-methacrylate) (PCMA) to synthesize well-defined block copolymers with a PEG block sheddable under acidic conditions. The chain extension polymerization kinetics showed known traits of RAFT polymerization. The molecular weight distributions of the copolymers prepared using the new macroRAFT agent remained below 1.2 during the polymerizations and the molecular weight of the copolymers was linearly proportional to monomer conversions. The acid-catalyzed hydrolysis behavior of the PEG-macroRAFT agent and the PEG-b-PtBMA (Mn = 13,600 by GPC, PDI = 1.10) was studied by GPC, 1H NMR and UV-vis spectroscopy. The half-life of acid-hydrolysis was 70 min at pH 2.2 and 92 h at pH 4.0. The potential use of the pH-labile shedding behavior of the copolymers was demonstrated by conjugating a thiol-modified siRNA to ω-pyridyldisulfide modified PEG-b-PCMA. The resultant PEG-b-PCMA-b-siRNA triblock modular polymer released PCMA-b-siRNA segment in acidic and siRNA segment in reductive conditions, as confirmed by polyacrylamide gel electrophoresis.