Preparation of Novel Nanostructures with High Light to Heat Conversion and Investigation of their Fhotothermal Efficiencies and Toxicities/Yakın Kızılötesi Bölgede Yüksek Işık-Isı Çevrimine Sahip Özgün Nanoyapıların Hazırlanması, Fototermal Etkinliklerinin ve Toksisitelerinin Araştırılması

Cancer is known as one of the main causes of death and according to Centers for Disease Control and Prevention Organization accounted for 8.2 million deaths worldwide in 2012 with an increasing incidence rate. For this reason, progressing efficient therapeutic strategies with low toxicities to eradicate tumours specificly, is considered as the main object in the cancer treatments. Poor specificity toward malignant tissues, systemic side effects, low efficacy and drug resistance are the well-known disadvantages of widely applied radiation and chemotherapies. Thus, to improve the cancer therapy, it is expected that the therapeutic methods should eliminate only diseased cells/tissues without causing collateral damage selectively. The development of new protocols for biomedical application are encouraged by advanced nanotechnologies and production of novel nanomaterials. When it is compared the conventional tratment like surgery, radiation therapy, and chemotherapy with nanoparticle approach, nanoparticle treatments are minimally invasive and should result in minimal side effects. Accordingly, novel and effective therapeutics with unique light-to-heat conversion property of nanoscale materials can be utilized for cancer treatment. Among them, near-infrared (NIR) region photothermal therapy (PTT) has become more popular and developed quickly due to minimally invasive treatments for patients. Generally, photothermal therapy depends on the photosensitizers taken up by cancer cells to transfer light to heat, leading to photoablation of the cells and subsequent cell death. Therefore, photosensitizing agents are a key factor in photothermal therapy. In PTT, due to its easy operation, ability to be locally focused on a specific region and minimal absorbance by skin and tissues to allow for noninvasive penetration of reasonably deep tissues, near-infrared (NIR) light (700–1000 nm) is preferred. Recently, due to their high photothermal conversion efficiency and the ease of synthesis and modification, inorganic based fotothermal therapy agents (PTA) have received great interest. Among them, gold nanoparticles (AuNPs) are considered as a special photosensitizer due to their strong localized surface plasmon resonance (LSPR). Different types of Au nanoparticle based photosensitizers in photothermal therapy, like nanorods, nanocages, and nano-core–shells, nanostars have been reported. Unfortunately, the problem related to the potential toxicity induced by photothermal agents (especially for carbon nanotubes or graphene, CTAB coated Au rods, copper sulfide crystals and iron oxide nanoparticles (Fe3O4 NPs), is still an unresolved debate, which will inevitably limit future clinic applications of PTT. Therefore, it is significant to explore an effective fototermal therapy agent in order to decrease the extra-high-dose nanoparticles used in photothermal ablation of cancer with NIR irradiation which can generate potential toxicity to the body. In addition, with the presence of effective agents in the near infrared region, deeper cases may be treated with photothermal therapy. In this project proposal, it is aimed to develop novel photothermal therapy agents, which can reduce toxic effect, using in very small quantities, by increasing the light to heat conversion efficiency and be able to provide treatment even in deeper case due to the effective light to heat conversion in the near infrared region (NIR) because of the different and improved plasmon resonance properties than the photothermal agents in the literature.For this it is planned to prepare 6 different phototermal agent and detection of the efficiencies of them in photothermal therapy. The first two of these structures will be formed by adding gold (AuNPs) and gold-silver bimetallic nanoparticles (AuAgNPs) of 1-3 nm in size onto the hollow gold nanoparticles (Hollow AuNPs) with a 60-100 nm size and 5-10 nm shell thickness (AuNPs/HollowAuNPs(1. agent), AuAgNPs/HollowAuNPs (2. agent)). The third and fourth agents will be prepared by adding gold nanoparticles and gold-silver bimetallic nanoparticles of 1-3 nm in size on magnetic iron oxide nanoparticles coated with a thin silica shell (AuNPs/Fe3O4-SiO2 (3. agent) ve AuAgNPs/Fe3O4-SiO2 (4. agent)). The proposed last two agents will be formed with the addition of gold nanoparticles and gold-silver bimetallic nanoparticles onto the resulting structure formed by the addition of gold shells over the thin silica layer coated iron oxide nanoparticles (AuNPs/AuShell/Fe3O4-SiO2 (5. agent), ve AuAgNPs/AuShell/Fe3O4-SiO2 (6. agent)). Characterization of the photothermal therapy agents will be done by using HR-TEM, XPS, VSM, ICP-OES, XRD, UV-Vis, Raman. The photothermal effects of the prepared structures will then be measured by using an 808 nm wavelength laser irradiation in solution and then their activity in the cancer cell line (in vitro) will be investigated. Finally, toxicity studies of photothermal agents will be carried out.