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原子空位工程化超薄三金属纳米酶具有抗炎和抗肿瘤性能,可用于治疗肠道疾病。

Atomic vacancies-engineered ultrathin trimetallic nanozyme with anti-inflammation and antitumor performances for intestinal disease treatment.

机构信息

Department of Ultrasound, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, PR China.

Materdicine Lab, School of Life Sciences, Shanghai University, Shanghai, 200444, PR China.

出版信息

Biomaterials. 2023 Aug;299:122178. doi: 10.1016/j.biomaterials.2023.122178. Epub 2023 May 27.

DOI:10.1016/j.biomaterials.2023.122178
PMID:37271027
Abstract

Colitis-associated colorectal cancer, which represents a highly aggressive subtypes of colorectal cancer, requires concurrent antitumor and anti-inflammation therapies in clinic. Herein, we successfully engineered RuPdNi ultrathin trimetallic nanosheets (TMNSs) by introducing diverse transition metal atoms into the structure of RuPd nanosheets. Density functional theory (DFT) calculations reveal that the elaborate introduction of transition metal Ru and Ni facilitates the formation of Ru-O and Ni-O bonds on the surface of TMNSs for efficient reactive oxygen species (ROS) and reactive nitrogen species (RNS) scavenging, respectively. Moreover, the engineered abundant atomic vacancies on their surface conspicuously improve the performance in eliminating reactive oxygen and nitrogen species (RONS). The designed TMNSs act as a multi-metallic nanocatalyst with RONS elimination performance for chronic colitis treatment by relieving inflammation, as well as photothermal conversion capability for colon cancer therapy by inducing hyperthermia effect. Profiting from the excellent RONS scavenging activities, TMNSs can down-regulate the expression levels of the pro-inflammatory factors, thereby leading to prominent therapeutic efficacy against dextran sulfate sodium-induced colitis. Benefiting from the high photothermal performance, TMNSs cause significant suppression of CT-26 tumors without obvious recurrence. This work provides a distinct paradigm to design multi-metallic nanozymes for colon disease treatment by elaborate introduction of transition metal atoms and engineering of atomic vacancies.

摘要

结直肠相关性大肠癌是一种侵袭性很强的结直肠癌亚型,临床上需要同时进行抗肿瘤和抗炎治疗。在此,我们通过将多种过渡金属原子引入 RuPd 纳米片的结构中,成功地设计了 RuPdNi 超薄三元纳米片(TMNSs)。密度泛函理论(DFT)计算表明,过渡金属 Ru 和 Ni 的精心引入有利于在 TMNSs 表面形成 Ru-O 和 Ni-O 键,从而分别有效地清除活性氧(ROS)和活性氮(RNS)。此外,在其表面设计的丰富原子空位显著提高了消除活性氧和氮物种(RONS)的性能。设计的 TMNSs 作为一种具有 RONS 消除性能的多金属纳米催化剂,通过缓解炎症来治疗慢性结肠炎,同时通过诱导热效应来实现光热转换能力以治疗结肠癌。受益于出色的 RONS 清除活性,TMNSs 可以下调促炎因子的表达水平,从而对葡聚糖硫酸钠诱导的结肠炎产生显著的治疗效果。受益于高的光热性能,TMNSs 可显著抑制 CT-26 肿瘤,且无明显复发。这项工作为通过精心引入过渡金属原子和工程原子空位来设计用于治疗结肠疾病的多金属纳米酶提供了一个明显的范例。

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