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    CD44 Targeting of Cisplatin-Loaded Hyaluronic Acid-Modified Mesoporous Silica Nanoparticles for Lung Adenocarcinoma: Synthesis, Characterization, In Vitro and In Vivo Evaluation
    (Mdpi, 2026) Guler, Cem; Gelen, S. Sacide; Sanci, Ebru; Buhur, Aylin; Tikir, H. Ece; Nalbantsoy, Ayse; Guner, Adem
    Background/Objectives: Cisplatin (CDDP) is widely used in the treatment of non-small cell lung cancer (NSCLC); however, its clinical efficacy is limited by severe systemic toxicity. Hyaluronic acid (HA) modification enables the targeting of CD44-overexpressing cancer cells, enhances biocompatibility, provides controlled drug release, and prolongs systemic circulation. This study aimed to develop high-molecular-weight hyaluronic acid-modified, cisplatin-loaded mesoporous silica nanoparticles (HA-MSN-CDDP) to selectively target CD44-overexpressing lung adenocarcinoma cells. Methods: HA-MSN-CDDP nanoparticles were synthesized via the sol-gel method and characterized by FTIR, DLS, SEM, and TEM methods. Antitumor efficacy was evaluated using both in vitro and in vivo xenograft lung cancer models in mice. Results: HA modification enabled controlled and sustained release of cisplatin from the HA-MSN-CDDP drug delivery system. Through HA-mediated receptor-dependent endocytosis, the nanoparticles exhibited enhanced cellular uptake and selective cytotoxicity toward CD44-positive cells. HA-MSN-CDDP significantly reduced the cytotoxic, genotoxic, and oxidative stress effects of free cisplatin on healthy cells while markedly enhancing apoptosis in A549-Luc-C8 cells. The system showed excellent hemocompatibility, supporting its potential for intravenous use. In vivo, HA-MSN-CDDP effectively suppressed tumor growth, mitigated lipid peroxidation, and preserved antioxidant enzyme activities (SOD and CAT) in major organs. Histological analyses confirmed reduced cisplatin-induced nephrotoxicity. Conclusions: HA-MSN-CDDP demonstrates strong potential as a targeted chemotherapeutic platform for NSCLC, combining high antitumor efficacy with reduced systemic toxicity.
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    Öğe
    In Silico and In Vitro Perspectives on the Potential Anticancer Activity and Toxicity of Anticancer Drug Modified with Carbohydrates Containing Novel Triazole Compounds
    (Wiley-V C H Verlag Gmbh, 2025) Gokmen, Buse; Guler, Cem; Sanci, Ebru; Demir, Ramiz; Karayildirim, Cinel Koksal; Alsakini, Karrar Ali Mohammed Hasan; Nalbantsoy, Ayse
    5-Fluorouracil (5-FU) is one of the first-line chemotherapeutic agents used in systemic therapy of solid tumors. However, several challenges restrict the use of 5-FU such as serious side effects and short plasma half-life. Because carbohydrates and 1,2,3-triazoles have various biological activities, they have been extensively used in medicine to obtain more effective anticancer drugs in recent years. The aim of this study is to modify 5-FU with carbohydrates containing 1,2,3-triazole compounds to reduce its toxic effect, and to reveal the anticancer properties of the obtained 5-FU derivatives. These derivatives (5-FU-I, 5-FU-II, and 5-FU-III) revealed dose-dependent cytotoxic effects on CaCo-2, PANC-1, and A549 cancer cells. It was determined that cytotoxic effects of the 5-FUs change dependent on used carbohydrate types, cell lines, and administered doses. These derivatives showed apoptotic and necrotic cell deaths which used to destroy the cancer cells. 5-FUs showed no genotoxic effect in the bacterial reverse mutasyon assay. They demonstrated strong antiangiogenic properties in the HET-CAM test. In silico study results demonstrated that carbohydrate modification can increase half-life and clearance, also decrease side effects of 5-FU. In silico data supported the in vitro findings and results demonstrated 5-FU derivatives were better drug candidates. Our results reveal that 5-FUs derivatives modified carbohydrates containing 1,2,3-triazole compounds have potential in cancer therapy.