Johari Behrooz, Tavangar-Roosta Shabnam, Gharbavi Mahmoud, Sharafi Ali, Kaboli Saeed, Rezaeejam Hamed
Zanjan Pharmaceutical Biotechnology Research Center, Zanjan University of Medical Sciences, Zanjan, Iran.
Department of Medical Biotechnology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.
Heliyon. 2024 Jul 4;10(13):e34096. doi: 10.1016/j.heliyon.2024.e34096. eCollection 2024 Jul 15.
Sox2 and Oct4 dysregulations could significantly increase in the cancer stem cell (CSC) population in some cancer cells and resistance to common treatments. In this study, the synergistic effects of Sox2-Oct4 decoy oligodeoxynucleotides-encapsulated Niosomes-zinc hybrid nanocarriers along with X-irradiation conditions as a combinational therapy tool were investigated in the treatment of cancer-like stem cells (NTERA-2). The NTERA-2 cell line known as a cancer-like stem cell line was used in this investigation. Sox2-Oct4 decoy oligodeoxynucleotides were designed based on the sequence of the Sox2 promoter and synthesized. Physicochemical characteristics of ODNs-encapsulated niosomes-zinc hybrid nanocarriers (NISM@BSA-DEC-Zn) investigated with FT-IR, DLS, FESEM, and ODNs release kinetic estimation assays. Further investigations such as hemolysis, uptake, cell viability, apoptosis, cell cycle, and scratch repair tests were performed. All the above assays were completed with and without X-ray exposure conditions (fractionated 2Gy). Physicochemical characteristics results showed that the Niosomes-Zn nanocarriers were successfully synthesized. NISM@BSA-DEC-Zn was efficiently taken up by NTERA-2 cells and significantly inhibited cell growth, increased apoptosis, and reduced cell migration in both conditions (with and without X-ray exposure). Furthermore, NISM@BSA-DEC-Zn treatment resulted in G1 and G2/M cell cycle arrest without and with X-irradiation, respectively. The prepared nanocarrier system can be a promising tool for drug delivery in cancer treatment. Decoy ODN strategy along with zinc nanoparticles could increase the sensitivity of cancer cells toward irradiation, which has the potential for combinational cancer therapies.
在某些癌细胞中,Sox2和Oct4的失调会显著增加癌症干细胞(CSC)群体,并导致对常规治疗产生抗性。在本研究中,研究了包裹Sox2-Oct4诱饵寡脱氧核苷酸的脂质体-锌杂化纳米载体与X射线照射条件作为联合治疗工具在治疗类癌干细胞(NTERA-2)中的协同作用。本研究使用了被称为类癌干细胞系的NTERA-2细胞系。基于Sox2启动子序列设计并合成了Sox2-Oct4诱饵寡脱氧核苷酸。通过傅里叶变换红外光谱(FT-IR)、动态光散射(DLS)、场发射扫描电子显微镜(FESEM)和寡脱氧核苷酸释放动力学估计试验研究了包裹寡脱氧核苷酸的脂质体-锌杂化纳米载体(NISM@BSA-DEC-Zn)的物理化学特性。还进行了溶血、摄取、细胞活力、凋亡、细胞周期和划痕修复试验等进一步研究。所有上述试验均在有和无X射线照射条件(分次给予2Gy)下完成。物理化学特性结果表明成功合成了脂质体-锌纳米载体。NISM@BSA-DEC-Zn被NTERA-2细胞有效摄取,在两种条件下(有和无X射线照射)均显著抑制细胞生长、增加凋亡并减少细胞迁移。此外,NISM@BSA-DEC-Zn处理分别在无X射线照射和有X射线照射时导致G1期和G2/M期细胞周期停滞。所制备的纳米载体系统可能是癌症治疗中一种有前景的药物递送工具。诱饵寡脱氧核苷酸策略与锌纳米颗粒相结合可提高癌细胞对辐射的敏感性,具有联合癌症治疗的潜力。