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Tumor microenvironment-responsive arsenic-loaded layered double hydroxides film with synergistic anticancer and bactericidal activity

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Abstract

Malignant obstruction makes gallbladder cancer have a high mortality rate. Nickel–titanium alloy (nitinol) stents are commonly used as a local intervention to maximize patient survival time, but the stents lack antitumor and antibacterial capacity and are vulnerable to secondary obstruction. Arsenic-based drugs show good therapeutic promise against gallbladder cancer. To meet clinical needs, the layered double hydroxides (LDHs) film is constructed on the nitinol, whose arsenite loading amounts rose by 60% after simple heat treatment compared with the conventional anion-exchange strategy. In addition, calcination promotes the dissolution of nickel ions from the LDHs lattice, resulting in a powerful synergistic killing effect on tumor cells together with the released arsenic. More importantly, the calcined arsenic-loaded LDHs are sensitive to the acidic microenvironment of tumor tissues, which presents a much lower arsenic and nickel release amount in the normal tissues, guaranteeing its biosafety. Meanwhile, the vertically sharp LDHs nanosheets can synergize with arsenic to achieve effective physical cleavage and chemical killing of adherent and planktonic bacteria. In short, we attempt to use arsenic drugs for local interventions and reasonably avoid their toxic side effects, which provides a new design idea for nitinol stents applied in the treatment of gallbladder cancer.

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摘要

恶性梗阻使得胆囊癌的死亡率很高。镍钛合金支架通常被用于局部介入治疗以最大限度地延长病人的生存时间, 但这种支架缺乏抗肿瘤和抗菌能力, 容易造成二次阻塞。砷类药物对胆囊癌显示出良好的治疗前景。为了满足临床需要, 在镍钛合金表面构建了层状双氢氧化物薄膜。与传统的阴离子交换策略相比, 经过简单的热处理后, LDHs对砷的负载量提升了60%。此外, 煅烧促进了镍离子从LDHs晶格释放, 与释放的砷一起对肿瘤细胞产生了强大的协同杀伤作用。更重要的是, 经过煅烧的含砷LDHs对肿瘤组织的酸性微环境敏感, 在正常组织中呈现出更低的砷和镍释放量, 保证了其生物安全性。同时, 垂直锋利的LDHs纳米片可以与砷协同作用, 实现对粘附和浮游细菌的有效物理切割和化学杀伤。总之, 这项工作尝试将砷类药物用于肿瘤局部介入治疗的同时合理地避免了砷的毒副作用, 为设计用于胆囊癌治疗的镍钛合金支架提供了新的思路。

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Acknowledgements

This study was financially supported by the National Natural Science Foundation of China (Nos. 31971249 and 51901239) and the Science and Technology Commission of Shanghai Municipality (Nos.19JC1415500 and 20S31903300).

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Authors and Affiliations

  1. State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, 200050, China

    Shun Xing, Hai-Feng Zhang, Li-Dan Liu, Cheng-Ce Li, Chao Wei, Jun-Yu Liu & Xuan-Yong Liu

  2. Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing, 100049, China

    Shun Xing, Hai-Feng Zhang, Li-Dan Liu, Cheng-Ce Li, Chao Wei & Xuan-Yong Liu

  3. Intervention Center, Eastern Hepatobiliary Surgery Hospital, The Third Affiliated Hospital of Naval Medical University, Shanghai, 200438, China

    Nai-Jian Ge

  4. School of Health Sciences and Biomedical Engineering, Hebei University of Technology, Tianjin, 300130, China

    Dong-Hui Wang

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  1. Shun Xing
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Xing, S., Wang, DH., Zhang, HF. et al. Tumor microenvironment-responsive arsenic-loaded layered double hydroxides film with synergistic anticancer and bactericidal activity. Rare Met. 43, 1207–1221 (2024). https://doi.org/10.1007/s12598-023-02466-y

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