Upconvertıng nanopartiküller kullanılarak biyoteknolojik enzim-ilaçlar için fonksiyonel taşıyıcı sistemlerin geliştirilmesi

L-Asparaginase (LASNase) is the key chemotherapeutic drug for the treatment of Acute Lymphatic Leukemia (ALL). The L-ASNase form modified with polyethylene glycol (PEG) is used to minimize the immune response in patients. However, the use and accessibility of this enzyme are limited due to its short plasma half-life and expensive. In addition, there is a need for new carrier systems that eliminate the loss of enzyme activity after enzyme immobilization. Within the scope of the thesis, for L-ASNase, one of the most important enzyme drugs used in the clinic, the preparation of biocompatible and functional end group UCNPs immobilization of the PEG-L-ASNase enzyme, triggering its activity by NIR effect and its mechanism was carried out. In addition, the in vitro biocompatibility properties of the prepared immobilized system were determined. In this study, NaYF4: Yb3+, Er3+ induced at 980 nm and NaYF4: Nd3+ Yb3+, Er3+, induced at 808 nm UCNPs were firstly synthesized by hydrothermal method, and their structural and thermal characterizations were performed with XRD, DLS, Zeta-meter, TEM, FTIR, TGA, XPS and fluorescence spectrometry. Immobilization of PEG-L-ASNase on UCNP modified with PEI, GPTMS, and ICPTES was carried out using physical (electrostatic) and chemical (covalent) methods. Later intensity, exposure time, and laser distance studies were performed as NIR triggering parameters for carrier platforms containing enzymes. Immobilization parameters (immobilization efficiency, optimum pH, temperature, thermal stability, reusability, in vitro half-life, storage stability, trypsin digestion, etc.) were examined in detail and compared with the free enzyme. In vitro toxicity studies for UCNPs and UCNP-PEG-L-ASNases were performed on the L-929 cell line. In the conclusion, PEG-L-ASNaz was immobilized to UCNPs that can be induced at 980 and 808 nm for the first time within the scope of this thesis, and it has been shown that the enzyme can be induced by NIR. A better carrier system (NaYF4:Nd3+, Yb3+, Er3+/ICPTES) than existing systems has been developed by reaching approximately 547% in the induction rates of L-ASNase enzyme activity with NIR. In addition, the fact that this carrier system appears to be a promising system for biotechnological enzyme drugs due to no toxic to humans.