Miao Zhaohua, Chen Sheng, Xu Cheng-Yan, Ma Yan, Qian Haisheng, Xu Yunjun, Chen Huajian, Wang Xianwen, He Gang, Lu Yang, Zhao Qingliang, Zha Zhengbao
School of Food and Biological Engineering , Hefei University of Technology , Hefei , Anhui 230009 , P. R. China . Email:
State Key Laboratory of Advanced Welding and Joining , Harbin Institute of Technology , Harbin , 150001 , P. R. China.
Chem Sci. 2019 Apr 23;10(21):5435-5443. doi: 10.1039/c9sc00729f. eCollection 2019 Jun 7.
A common issue of functional nanoagents for potential clinical translation is whether they are biodegradable or renal clearable. Previous studies have widely explored noble metal nanoparticles (Au and Pd) as the first generation of photothermal nanoagents for cancer therapy, but all of the reported noble metal nanoparticles are non-degradable. On the other hand, rhenium (Re), one of the noble and precious metals with a high atomic number ( = 75), has been mainly utilized as a jet superalloy or chemical catalyst, but the biological characteristics and activity of Re nanoparticles have never been evaluated until now. To address these issues, here we report a simple and scalable liquid-reduction strategy to synthesize PEGylated Re nanoclusters, which exhibit intrinsically high photothermal conversion efficacy (33.0%) and high X-ray attenuation (21.2 HU mL mg), resulting in excellent photothermal ablation (100% tumor elimination) and higher CT enhancement (15.9 HU mL mg for commercial iopromide in clinics). Impressively, biocompatible Re nanoclusters can degrade into renal clearable ReO ions after exposure to HO, and thus achieve much higher renal clearance efficiency than conventional gold nanoparticles. This work reveals the potential of theranostic application of metallic Re nanoclusters with both biodegradation and renal clearance properties and provides insights into the design of degradable metallic platforms with high clinical prospects.
功能性纳米制剂在临床转化中面临的一个常见问题是它们是否可生物降解或可通过肾脏清除。先前的研究广泛探索了贵金属纳米颗粒(金和钯)作为第一代用于癌症治疗的光热纳米制剂,但所有报道的贵金属纳米颗粒都不可降解。另一方面,铼(Re)是一种原子序数较高( = 75)的贵金属,主要用作喷气式高温合金或化学催化剂,但直到现在,铼纳米颗粒的生物学特性和活性从未被评估过。为了解决这些问题,我们在此报告一种简单且可扩展的液相还原策略,用于合成聚乙二醇化铼纳米团簇,该纳米团簇具有内在的高光热转换效率(33.0%)和高X射线衰减(21.2 HU mL mg),从而实现出色的光热消融(100%肿瘤消除)和更高的CT增强效果(临床上用于商业碘普罗胺的为15.9 HU mL mg)。令人印象深刻的是,生物相容性铼纳米团簇在暴露于H₂O₂后可降解为可通过肾脏清除的ReO₄⁻离子,因此比传统金纳米颗粒具有更高的肾脏清除效率。这项工作揭示了具有生物降解和肾脏清除特性的金属铼纳米团簇在诊疗应用中的潜力,并为设计具有高临床前景的可降解金属平台提供了见解。