نانوپلتفرم هاي سيليكاتي متخلخل اصلاح شده با پيش ماده هاي هيدروكسي آپاتيت و شبكه هاي فلز- فنولي يا فوليك اسيد، و بررسي كاربردهاي آن ها در پركننده هاي استخوان، نور پويا درماني، و رديابي دارورساني بر پايه كارمنيك اسيد؛ كمپلكس نيكل(II) كارمنيك اسيد به عنوان داروي ضد سرطان استخوان

Diseases such as various types of bone fractures, bone marrow cancer, an‎d bone infections are among the factors that damage bones. The importance of bones, has led to significant deman‎d for treatment of these diseases. However, the hierarchical structure of bone, makes the design of therapeutic methods problematic. Hence, this thesis focuses on the study, design, an‎d synthesis of biomaterials based on natural compounds for multifunctional applications in the treatment of bone diseases.In the first study, porous silica nanoparticles containing hydroxyapatite precursors were prepared an‎d coated with a metal-phenolic network formed from magnesium ions an‎d pomegranate extract. After precise characterization of the synthesized core-shell nanoparticles by using identification methods such as FE-SEM, TEM, BET-BJH, XPS, an‎d FT-IR, it was determined that these nanoparticles have a porous, spherical, core-shell structure with a particle size of 89 nanometers. Their cytotoxicity, biocompatibility, an‎d osteoinductivity were then investigated. Based on these results, the synthesized nanoparticles are biocompatible an‎d bioactive, capable of inducing bone differentiation in dental pulp stem cells, an‎d they prevent the growth of E. coli an‎d S. aureus bacteria.Since cancer is one of the main life-threatening diseases, in the second part, continuing our previous research, where carminic acid molecules were loaded as drugs into folic acid-modified silica nanoparticles, the optimal drug loading amount, drug release mechanism, an‎d cytotoxic effects on cervical cancer (HeLa) an‎d leukemia (K-562) cells were studied. However, the synergistic effect of carminic acid an‎d folic acid molecules in cancer treatment like, their optical properties, an‎d the mechanism of cell death in cancer cells induced by designed nanosystem remained unknown. Therefore, in the second study, aiming to answer these questions, the anticancer properties of the natural compound carminic acid, extracted from a type of insect named “cochineal”, which is structurally similar to the drug doxorubicin, were first studied using molecular docking. Subsequently, the optical properties of this molecule an‎d the effect of folic acid on these properties were investigated. Then, the ability of carminic acid to interact with DNA an‎d topoisomerase I an‎d II enzymes, as well as to generate reactive oxygen species to induce cell death in cancer cells, was eva‎luated by designing a novel method based on the dot-blot technique. The efficiency of these nanoparticles in drug delivery tracking was also studied. The results of these studies led to transforming a conventional nanocarrier to a multifunctional therapeutic nanoplatform for photodynamic ROS generation an‎d FRET-based tracking. In the third part, considering the importance of treating osteosarcoma, an‎d the evidence in the efficacy of carminic acid in cancer treatment, a nickel complex with carminic acid ligan‎d was synthesized. Computational chemistry methods an‎d characterization techniques such as VSM, FT-IR, ICP-OES, CHN, ESI-Mass, an‎d UV-Vis absorption an‎d fluorescence emission spectroscopy were used to identify the octahedral structure of this paramagnetic complex. Its efficacy in treating osteosarcoma was then investigated using the MTT assay. Additionally, the generation of reactive oxygen species under visible light irradiation an‎d in dark conditions was investigated using a fluorometric assay with the DCF fluorescent molecule. The interaction of this complex with the telomeric region of DNA was also studied using molecular docking. Based on the conducted studies, the nickel (II) complex with carminic acid ligan‎d can induce oxidative stress in cancer cells without the need for light irradiation an‎d by interacting with the telomeric region of DNA, it can cause cell death in MG-63 an‎d SH-SY5Y cells involved in bone cancer, while not harming healthy MCF-10A cells.

حسن حداد زاده , زهره ميراحمدي زارع

حسين فرخ پور

شهرام تنگستاني نژاد , علي حسين كيانفر , غلامحسين محمدنژاد شيرازي