Biyomühendislik Ana Bilim Dalı Tez Koleksiyonu
Permanent URI for this collectionhttps://hdl.handle.net/20.500.12573/417
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Browsing Biyomühendislik Ana Bilim Dalı Tez Koleksiyonu by Author "Bayram, Nazende Nur"
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doctoralthesis.listelement.badge Development of breast cancer targeted, multifunctional cross-linked micelle nanocarriers(Abdullah Gül Üniversitesi, Fen Bilimleri Enstitüsü, 2023) Bayram, Nazende Nur; AGÜ, Fen Bilimleri Enstitüsü, Biyomühendislik Ana Bilim DalıIn this thesis, we developed two different micelle-based nanocarriers, which are pH-responsive and core cross-linked micelle (CCMs), and specifically target HER2 receptor on breast cancer cells. Intracellularly degradable and stabilized micelles were prepared by core cross-linking and RAFT polymerization in the presence of an acid-sensitive cross-linker. Poly(OEGMA) and poly(SBMA) were used as shell parts of these micelles in order to compare the effect of hydrophilic coatings on nanocarrier characteristics. In the first design, we applied drug conjugation (Doxorubicin) with a cleavable linker while in the second design, we used the encapsulation method for drug loading. Targeted micelles were obtained by coupling of HER2-specific peptides (VSSTQDFP and LTVSPWY) and antibody (Herceptin) to POEGMA and poly (SBMA) based CCMs, respectively. These nanocarriers are designed to be stable in blood circulation but cleavable intracellulary to achieve controlled drug release. Nanocarriers were characterized structurally by FTIR and 1H-NMR spectroscopies for all synthesis and conjugation steps. Moreover, nanocarriers and drug-loaded formulations were investigated by Zetasizer, Nanosight, and TEM/SEM analysis. The results showed that designed nanocarriers have a very high potential for HER2-specific targeted drug release for the treatment of breast cancer. This thesis holds significant importance due to its successful demonstration of two distinct systems exhibiting high stability, pH sensitivity, and high selectivity for HER2-targeted therapy of breast cancer.