Institute of Frontier and Interdisciplinary Science, Shandong University, Qingdao, 266237, P. R. China.
State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130 022, China.
Small. 2023 Jul;19(29):e2300370. doi: 10.1002/smll.202300370. Epub 2023 Apr 8.
Ion-interference therapy (IIT) utilizes ions to disturb intracellular biological processes and has been received increasing attention in tumor treatments recently. However, the low therapeutic efficiency still hinders its further biological applications. Herein, via a simple and one-pot gas diffusion process, polyethylene glycol (PEG)-modified Mn ions and usnic acid (UA)-incorporated CaCO nanomaterials ( CaMnUA) as Ca /Mn ions reservoirs are prepared for magnetic resonance imaging (MRI)-guided UA-elevated IIT. Among CaMnUA, UA not only increases cytoplasmic Ca ions to amplify Ca overload caused by CaCO decomposition, but also enhances Mn ions-participated Fenton-like biocatalysis by intracellular H O generation and glutathione consumption. Then increasing the intracellular oxidative stress and decreasing the triphosadenine supply induce apoptosis together, resulting in UA-boosted IIT. The simple and efficient design of the dual ions reservoirs will contribute to improve the antitumor activity of IIT and further development of calcium-based nanomaterials in the future.
离子干扰疗法（IIT）利用离子来干扰细胞内的生物过程，最近在肿瘤治疗中受到越来越多的关注。然而，低治疗效率仍然阻碍了其在生物学中的进一步应用。在此，通过一种简单的一步气相扩散法，制备了聚乙二醇（PEG）修饰的 Mn 离子和含有乌头酸（UA）的 CaCO 纳米材料（CaMnUA）作为 Ca/Mn 离子的储库，用于磁共振成像（MRI）引导的 UA 升高的 IIT。在 CaMnUA 中，UA 不仅增加细胞质中的 Ca 离子，以放大 CaCO 分解引起的 Ca 过载，还通过细胞内 H2O2 的产生和谷胱甘肽的消耗，增强 Mn 离子参与的类芬顿生物催化作用。然后，增加细胞内氧化应激和减少三磷酸腺苷的供应共同诱导细胞凋亡，导致 UA 增强的 IIT。这种双离子储库的简单高效设计将有助于提高 IIT 的抗肿瘤活性，并为未来基于钙的纳米材料的发展做出贡献。
