Determination of drug transport capacity of functionalized mesoporous silica materials and exami̇nati̇on of thei̇r in vitro effects on PC3 cell line
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Abstract (EN)
Prostate cancer is one of the most common and lethal types of cancer among men worldwide, ranking sixth among cancer-related deaths in males. Chemotherapy remains one of the primary treatment options for prostate cancer. However, a major drawback of chemotherapeutic agents is their lack of selectivity, often targeting not only cancerous cells but also healthy tissues, thereby leading to severe systemic side effects. As a result, drug delivery systems have recently emerged as promising alternative strategies in cancer therapy. In this context, mesoporous silica-based materials have garnered significant attention due to their outstanding physicochemical properties for drug delivery applications. These materials offer numerous advantages such as high specific surface area, large pore volume, uniform pore size distribution, high biocompatibility, and low toxicity. In this study, SBA-15 type mesoporous silica was selected as a drug carrier system. Owing to its well-ordered hexagonal pore structure, SBA-15 provides a suitable platform for the controlled release of therapeutic agents.The morphology, mesostructure and funcitionality of the metarials were characterized by scanning electron microscopy, small-angle X-ray scattering, nitrogen adsorption-desorption, Fourier transform infrared spectroscopy. Surface area was determined by BET (Brunauer–Emmett–Teller) method and average pore size and volume were determined by BJH (Barret-Hoyner-Halenda) method. SBA-15, whose structural suitability was confirmed, was then modified with various functional groups. The biological activity of functionalized SBA-15 structures was assessed through in vitro cytotoxicity assays using L929 (healthy mouse fibroblast) and PC-3 (human prostate cancer) cell lines. In cell culture experiments, PC-3 cells were maintained in RPMI-1640 medium supplemented with 10% Fetal Bovine Serum (FBS) and gentamicin, while L929 cells were cultured in DMEM high glucose medium containing 10% FBS and penicillin. Cell viability was evaluated using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay across a concentration range of 6.17–166.6 µg/mL. Concentrations that preserved cell viability above 80% were considered biocompatible. SBA-15 particles were subsequently loaded with doxorubicin (DOX) at these concentrations and applied to both cell lines. The results revealed that functionalized SBA-15 structures exhibited selective cytotoxicity toward PC-3 cancer cells, while exerting no significant toxicity on healthy L929 cells. This suggests that surface functional groups may facilitate selective interactions by recognizing biochemical differences between cancerous and healthy cells. Furthermore, DOX-loaded non-functionalized SBA-15 structures induced dose-dependent cytotoxicity in PC-3 cells, while maintaining high cell viability in L929 cells. This effect is likely due to the drug release behavior of the system, where DOX is preferentially released in the tumor microenvironment. The calculated selectivity index (SI) of approximately 1.8, based on IC₅₀ values, quantitatively supports the anticancer specificity of the system. In conclusion, this study demonstrates that both surface-functionalized SBA-15 structures and DOX-loaded SBA-15 carriers exhibit selective behavior through different mechanisms—either via biological recognition or controlled release—and may serve as promising, safe, and target-oriented drug delivery platforms for prostate cancer therapy.
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Eda Gülşah Erdağ
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Eda Gülşah Erdağ (Master Thesis). Determination of drug transport capacity of functionalized mesoporous silica materials and exami̇nati̇on of thei̇r in vitro effects on PC3 cell line, 2025, Selçuk University.
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