Molecular Tumor Biology, Department of Otorhinolaryngology, Head and Neck Surgery, University Medical Centre of the Johannes Gutenberg University, 55131, Mainz, Germany.
Institute of Inorganic Chemistry and Analytical Chemistry, Johannes Gutenberg University, 55128, Mainz, Germany.
J Trace Elem Med Biol. 2019 Jan;51:226-234. doi: 10.1016/j.jtemb.2018.08.002. Epub 2018 Aug 7.
The predicted global cancer burden is expected to surpass 20 million new cancer cases by 2025. Despite recent advancement in tumor therapy, a successful cancer treatment remains challenging. The emerging field of nanotechnology offers great opportunities for diagnosis, imaging, as well as treatment of cancer. Zinc oxide nanoparticles (ZnO NP) were shown to exert selective cytotoxicity against tumor cells via a yet unknown mechanism, most likely involving the generation of reactive oxygen species (ROS). These nanoparticles are a promising therapeutic opportunity as zinc is a nontoxic trace element and its application in medically-related products is considered to be safe. We could show that ZnO NP can exert cytotoxic effects on several human tumor cell lines. There can be found ZnO NP concentrations which selectively damage tumor cells while human fibroblasts do not sustain lasting damage. Cytotoxicity is attributable to the release of zinc ions from the nanoparticles outside the cells as well as to a direct cell-nanoparticle interaction. This involves uptake of the particles into the tumor cells. With a silica shell the cytotoxicity can be delayed which can help in the future for a safe transport in the blood stream. Cellular damage finally cumulates in apoptotic cell death via zinc overload within 48 h after treatment with ZnO NP. A therapeutical perspective could be the targeted accumulation of ZnO NP at the tumor side to induce local zinc overload that substantially damages the tumor cells with no or low side effects. We suggest further studies to explore the potential of ZnO NP as an innovative anti-tumor agent.
预计到 2025 年，全球癌症负担将超过 2000 万例新癌症病例。尽管肿瘤治疗最近取得了进展，但成功治疗癌症仍然具有挑战性。新兴的纳米技术领域为癌症的诊断、成像以及治疗提供了巨大的机会。氧化锌纳米粒子（ZnO NP）通过一种未知的机制对肿瘤细胞表现出选择性细胞毒性，很可能涉及活性氧物质（ROS）的产生。这些纳米粒子是一种很有前途的治疗机会，因为锌是一种无毒的微量元素，其在医学相关产品中的应用被认为是安全的。我们可以证明 ZnO NP 可以对几种人类肿瘤细胞系发挥细胞毒性作用。存在 ZnO NP 浓度选择性地破坏肿瘤细胞而不会对人类成纤维细胞造成持久损害。细胞毒性归因于细胞外纳米粒子中锌离子的释放以及直接的细胞-纳米粒子相互作用。这涉及到将颗粒摄取到肿瘤细胞中。用二氧化硅壳可以延迟细胞毒性，这有助于将来在血液中安全运输。细胞损伤最终通过锌超载在治疗后 48 小时内累积导致细胞凋亡死亡与 ZnO NP。一种治疗方法是将 ZnO NP 靶向积聚在肿瘤部位，以诱导局部锌超载，从而对肿瘤细胞造成实质性损伤，而副作用很小或没有。我们建议进一步研究探索 ZnO NP 作为一种创新的抗肿瘤剂的潜力。
