Danişman-Kalindemirtaş Ferdane, Özerkan Dilşad, Kariper İshak Afşin, Erdemir Cilasun Gökçe, Ülküseven Bahri, Erdem-Kuruca Serap
Department of Physiology, Faculty of Medicine, Erzincan Binali Yildirim University, Erzincan.
Department of Genetic and Bioengineering, Faculty of Engineering and Architecture, Kastamonu University, Kastamonu.
Anticancer Drugs. 2025 Mar 1;36(3):208-219. doi: 10.1097/CAD.0000000000001679. Epub 2025 Jan 6.
This study explores the therapeutic potential of albumin-bound Zn(II)-thiosemicarbazone compounds (Alb-ZnTcA, Alb-ZnTcB) against breast cancer cells. Previous research indicates that these compounds hinder cancer cell proliferation by blocking DNA synthesis, promoting oxidative stress to induce apoptosis, and disrupting the cell cycle to inhibit cellular division. This study focuses on the loading and characterization of these potentially chemically unstable compounds on bovine serum albumin-based nanocarriers. Accordingly, unlike previous studies using albumin nanoparticles, in this study, ultraviolet light was used to precisely bind the therapeutic agent to albumin during the integration of thiosemicarbazones, achieving controlled nanoparticle size to control nanoparticle size. The mean diameter of Alb-ZnTcA nanoparticles was 32 nm, while Alb-ZnTcB exhibited an average diameter of 43 nm. Notably, Alb-ZnTcA displayed the highest cytotoxicity toward breast cancer cells, suggesting an optimal size for cellular uptake. Additionally, albumin-bound compounds showed enhanced cytotoxicity at lower concentrations, potentially minimizing adverse side effects. Apoptosis analysis indicated that both Alb-ZnTcA and Alb-ZnTcB induce cell death predominantly through apoptosis, effectively preventing the uncontrolled proliferation of cancer cells. These findings demonstrate the potential of Zn(II)-thiosemicarbazone compounds loaded on albumin-based nanocarriers for breast cancer treatment. The increased potency of Alb-ZnTcA and Alb-ZnTcB compared to free compounds, along with their ability to activate apoptotic signaling pathways in MCF-7 breast cancer cells, highlights a promising approach for future cancer therapies. This study suggests that albumin-bound Zn(II)-thiosemicarbazone compounds could offer a targeted and effective strategy in breast cancer treatment, leveraging the advantages of nanocarrier-based delivery systems.
本研究探讨了白蛋白结合的Zn（II）-硫代半卡巴腙化合物（Alb-ZnTcA、Alb-ZnTcB）对乳腺癌细胞的治疗潜力。先前的研究表明，这些化合物通过阻断DNA合成、促进氧化应激以诱导细胞凋亡以及扰乱细胞周期以抑制细胞分裂来阻碍癌细胞增殖。本研究重点关注这些潜在化学不稳定化合物在基于牛血清白蛋白的纳米载体上的负载和表征。因此，与先前使用白蛋白纳米颗粒的研究不同，在本研究中，在硫代半卡巴腙整合过程中使用紫外线将治疗剂精确地结合到白蛋白上，实现了对纳米颗粒大小的控制。Alb-ZnTcA纳米颗粒的平均直径为32 nm，而Alb-ZnTcB的平均直径为43 nm。值得注意的是，Alb-ZnTcA对乳腺癌细胞表现出最高的细胞毒性，表明其具有细胞摄取的最佳尺寸。此外，白蛋白结合的化合物在较低浓度下表现出增强的细胞毒性，可能将副作用降至最低。细胞凋亡分析表明，Alb-ZnTcA和Alb-ZnTcB均主要通过细胞凋亡诱导细胞死亡，有效阻止癌细胞的不受控制增殖。这些发现证明了负载在基于白蛋白的纳米载体上的Zn（II）-硫代半卡巴腙化合物在乳腺癌治疗中的潜力。与游离化合物相比，Alb-ZnTcA和Alb-ZnTcB效力的提高，以及它们在MCF-7乳腺癌细胞中激活凋亡信号通路的能力，凸显了一种未来癌症治疗的有前景的方法。本研究表明，白蛋白结合的Zn（II）-硫代半卡巴腙化合物可以利用基于纳米载体的递送系统的优势，在乳腺癌治疗中提供一种靶向且有效的策略。
