Research Project: Trail ile Uyarılmış Gliyoblastom Multiform (Gbm) Terapisi için biyoyapışkan Creka-Peg-Kitosan Nanoparçacıkların Tasarımı
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Contributors
Funders
ID
TB.00306
Authors
Kızılel, Seda
Faculty Member
Publications
Deep insight into PEGylation of bioadhesive chitosan nanoparticles: sensitivity study for the key parameters through artificial neural network model
(American Chemical Society, 2018) Bozüyük, Uğur; Doğan, Nihal Olcay; Kızılel, Seda; Department of Chemical and Biological Engineering; Yes; College of Engineering
lonically cross-linked chitosan nanoparticles have great potential in nanomedicine due to their tunable properties and cationic nature. However, low solubility of chitosan severely limits their potential clinical translation. PEGylation is a well-known method to increase solubility of chitosan and chitosan nanoparticles in neutral media; however, effect of PEG chain length and chitosan/PEG ratio on particle size and zeta potential of nanoparticles are not known. This study presents a systematic analysis of the effect of PEG chain length and chitosan/PEG ratio on size and zeta potential of nanoparticles. We prepared PEGylated chitosan chains prior to the nanoparticle synthesis with different PEG chain lengths and chitosan/PEG ratios. To precisely estimate the influence of critical parameters on size and zeta potential of nanoparticles, we both developed an artificial neural network (ANN) model and performed experimental characterization using the three independent input variables: (i) PEG chain length, (ii) chitosan/PEG ratio, and (iii) pH of solution. We studied the influence of PEG chain lengths of 2, 5, and 10 kDa and three different chitosan/PEG ratios (25 mg chitosan to 4, 12, and 20 mu moles of PEG) for the synthesis of chitosan nanoparticles within the pH range of 6.0-7.4. Artificial neural networks is a modeling tool used in nanomedicine to optimize and estimate inherent properties of the system. Inherent properties of a nanoparticle system such as size and zeta potential can be estimated based on previous experiment results, thus, nanoparticles with desired properties can be obtained using an ANN. With the ANN model, we were able to predict the size and zeta potential of nanoparticles under different experimental conditions and further confirmed the cell-nanoparticle adhesion behavior through experiments. Nanoparticle groups that had higher zeta potentials promoted adhesion of HEK293-T cells to nanoparticle-coated surfaces in cell culture medium, which was predicted through ANN model prior to experiments. Overall, this study comprehensively presents the PEGylation of chitosan, synthesis of PEGylated chitosan nanoparticles, utilizes ANN model as a tool to predict important properties such as size and zeta potential, and further captures the adhesion behavior of cells on surfaces prepared with these engineered nanoparticles.
Characterizing the cellular response to nitrogen-doped carbon nanocups
(Multidisciplinary Digital Publishing Institute (MDPI), 2019) Ayhan, Ceyda Açılan; Griffith, Amber S.; Zhang, Thomas D.; Burkert, Seth C.; Adıgüzel, Zelal; Star, Alexander; Saunders, William S.; Department of Molecular Biology and Genetics; School of Medicine; Yes; College of Sciences; SCHOOL OF MEDICINE
Carbon nanomaterials, specifically, carbon nanotubes (CNTs) have many potential applications in biology and medicine. Currently, this material has not reached its full potential for application due to the potential toxicity to mammalian cells, and the incomplete understanding of how CNTs interface with cells. The chemical composition and structural features of CNTs have been shown to directly affect their biological compatibility. The incorporation of nitrogen dopants to the graphitic lattice of CNTs results in a unique cup shaped morphology and minimal cytotoxicity in comparison to its undoped counterpart. In this study, we investigate how uniquely shaped nitrogen-doped carbon nanocups (NCNCs) interface with HeLa cells, a cervical cancer epithelial cultured cell line, and RPE-1 cells, an immortalized cultured epithelial cell line. We determined that NCNCs do not elicit a cytotoxic response in cells, and that they are uptaken via endocytosis. We have conjugated fluorescently tagged antibodies to NCNCs and shown that the protein-conjugated material is also capable of entering cells. This primes NCNCs to be a good candidate for subsequent protein modifications and applications in biological systems.
Light-triggered drug release from 3D-printed magnetic chitosan microswimmers
(American Chemical Society, 2018) Bozüyük, Uğur; Kızılel, Seda; Yasa, Oncay; Yasa, Immihan Ceren; Ceylan, Hakan; Sitti, Metin; Department of Chemical and Biological Engineering; Yes; College of Engineering
Advances in design and fabrication of functional micro/nanomaterials have sparked growing interest in creating new mobile microswimmers for various healthcare applications, including local drug and other cargo (e.g., gene, stem cell, and imaging agent) delivery. Such microswimmer-based cargo delivery is typically passive by diffusion of the cargo material from the swimmer body; however, controlled active release of the cargo material is essential for on-demand, precise, and effective delivery. Here, we propose a magnetically powered, double-helical microswimmer of 6 pm diameter and 20 pm length that can on-demand actively release a chemotherapeutic drug, doxorubicin, using an external light stimulus. We fabricate the microswimmers by two-photon-based 3D printing of a natural polymer derivative of chitosan in the form of a magnetic polymer nanocomposite. Amino groups presented on the microswimmers are modified with doxorubicin by means of a photocleavable linker. Chitosan imparts the microswimmers with biocompatibility and biodegradability for use in a biological setting. Controlled steerability of the microswimmers is shown under a 10 mT rotating magnetic field. With light induction at 365 nm wavelength and 3.4 X 10(-1) W/cm(2) intensity, 60% of doxorubicin is released from the microswimmers within 5 min. Drug release is ceased by controlled patterns of light induction, so as to adjust the desired release doses in the temporal domain. Under physiologically relevant conditions, substantial degradation of the microswimmers is shown in 204 h to nontoxic degradation products. This study presents the combination of light-triggered drug delivery with magnetically powered microswimmer mobility. This approach could be extended to similar systems where multiple control schemes are needed for on-demand medical tasks with high precision and efficiency.
Harnessing the immunomodulatory potential of chitosan and its derivatives for advanced biomedical applications
(Elsevier, 2025) Kızılel, Seda; Kebabcı, Aybaran Olca; Duymaz, Doğukan; Department of Chemical and Biological Engineering; Yes; Duymaz, Doğukan; Kebabcı, Aybaran Olca; College of Engineering
The success of biomaterial applications in medicine, particularly in tissue engineering, relies on achieving a balance between promoting tissue regeneration and controlling the immune response. Due to its natural origin, high biocompatibility, and versatility, chitosan has emerged as a promising biomaterial especially for immunomodulation purposes. Immunomodulation, refers to the deliberate alteration of the immune system's activity to achieve a desired therapeutic effect either by enhancing or suppressing the function of specific immune cells, signaling pathways, or cytokine production. This modulation opens up the unlimited possibilities for the use of biomaterials, especially about the use of natural polymers such as chitosan. Although numerous chitosan-based immunoregulatory strategies have been demonstrated over the past two decades, the lack of in-depth exploration hinders the full potential of strategies that include chitosan and its derivatives in biomedical applications. Thus, in this review, the possible immunomodulatory effects of chitosan, chitosan derivatives and their potential combined with various agents and therapies are investigated in detail. Moreover, this report includes agents for localized immune response control, chitosan-based strategies with complementary immunomodulatory properties to create synergistic effects that will influence the success of cell therapies for enhanced tissue acceptance and regeneration. Finally, the challenges and outlook of chitosan-based therapies as a powerful tool for improving immunomodulatory applications are discussed for paving the way for further studies.
