Fabrication of a Tubular CuO/NiO Biomimetic Nanozyme with Synergistically Promoted Peroxidase-like Performance for Isoniazid Sensing

Abstract

Isoniazid is an antibiotic primarily used in clinical treatment of tuberculosis, but excessive usage can lead to serious consequences such as hepatotoxicity, neurotoxicity, and even coma and death. Therefore, it is critical to exploit a quick, facile, and acute way for isoniazid analysis. In this work, we have demonstrated an efficient electrospinning–carbonation–wet chemistry reaction–calcination process to fabricate CuO/NiO nanotubes (NTs) as a promising nanozyme for peroxidase (POD) mimicking. In virtue of the distinct tubular structure and synergy between CuO and NiO from the mechanisms of both electron transfer and hydroxyl radical generation, a remarkably improved catalytic activity is realized for the CuO/NiO NTs compared with bare CuO and NiO samples. According to the admirable POD-like property, a rapid colorimetric detection for isoniazid is accomplished with a detection limit of 0.4 μM (S/N = 3) and favorable selectivity. In addition, the sensing capability of isoniazid in a real sample is also investigated with satisfactory results. This work offers a novel tactic to fabricate high-performance nanozymes with efficient isoniazid sensing capabilities to address challenges in disease treatment efficacy and public safety monitoring.

Copper-based Nanozymes: Properties and Applications in Biomedicine

“…Chang 等 [81] [62,93] 。Cheng 等 [94] 利用介孔 CuO 空心球的类 POD 活性构建纸质传感器，实现 H2O2 的直接检测(图 4(a)) 。以抗坏血酸、多种氨基酸和多种金属离子等 作为干扰物来检测该传感器的选择性，作者发现其 对 H2O2 具有超高选择性，对 H2O2 的检测下限达到 2.4 μmol/L，这能够满足生物分析等领域的需求(图 4(b))。 Zhu 等 [95] 基于 CuO/NiO 纳米管(NTs)的类 POD 活性和异烟肼的酰肼基团抑制 3,3',5,5'-四甲基 联苯胺(TMB)氧化的原理，实现对异烟肼的间接 比色检测。随着异烟肼浓度的增高，氧化型 TMB (oxTMB)在 652 nm 处的特征吸收值逐渐降低(图 4(c))。 CuO/NiO NTs 对异烟肼的线性检测范围为 1~ 20 μmol/L，检测限为 0.4 μmol/L(图 4(d))。 图 4 铜基纳米酶在生物传感中的应用 [94][95][96][97] Fig. 4 Cu-based nanozymes for biosensing [94][95][96][97] (a) Schematic diagram of a paper sensor for H2O2 detection based on mesoporous CuO hollow sphere nanozymes; (b) Effects of different substrates H2O2, ascorbic acid, Cys, Gly, Pro, Ala, Glu, GSH, Glc, Na + , K + , Ca 2+ , Mg 2+ , and Mn 2+ on the sensing performance of the paper sensor [94] ; (c) UV-Vis spectra of the mixed reaction system with CuO/NiO NTs, TMB, H2O2 and different concentrations of isoniazid.…”

“…4 Cu-based nanozymes for biosensing [94][95][96][97] (a) Schematic diagram of a paper sensor for H2O2 detection based on mesoporous CuO hollow sphere nanozymes; (b) Effects of different substrates H2O2, ascorbic acid, Cys, Gly, Pro, Ala, Glu, GSH, Glc, Na + , K + , Ca 2+ , Mg 2+ , and Mn 2+ on the sensing performance of the paper sensor [94] ; (c) UV-Vis spectra of the mixed reaction system with CuO/NiO NTs, TMB, H2O2 and different concentrations of isoniazid. (d) Dose response curve of sensing isoniazid [95] ; (e) Schematic illustration of the three-enzyme system (ACC) containing acetylcholinesterase (AchE), cholesterol oxidase (ChOx), and Cu-N-C single atom enzymes (SAzymes) for the organophosphorous pesticide (OP) detection; (f) Change of the absorbance at 652 nm of the ACC system with the addition of OP from 1 to 300 ng/mL; (g) Linear relationship between the inhibition rate (IR) of AchE and the logarithm of OP concentration [96] ; (h) Schematic illustration of CuO NPs for ascorbic acid and ALP detection; (i) Emission spectra of different detection systems, with a-d indicating AAP-TA-CuO NPs, ALP-TA-CuO NPs, AAP-ALP-TA-CuO NPs, and TA-AA-CuO NPs, respectively; (j) Linear relationship between emission intensity and concentration of ascorbic acid; (k) Calibration plot for ALP determination with different concentrations [97] TMB: 3,3′,5,5′-tetramethylbenzidine; GSH: Glutathione; AChE: Acetylcholinesterase; OP: Organophosphorus pesticide; AAP: L-ascorbate-2-trisodium Phosphate; TA: Terephthalic acid; ALP: Alkaline phosphatase; µM: µmol/L; mM: mmol/L 利用铜基纳米酶的类 POD 活性还可以实现对 能产生 H2O2 的生物分子的检测。Wu 等 [96] [99] 构 建 的 富 铜 普 鲁 士 蓝 纳 米 酶 (HPP@Cu NZs)能够降低氧化应激水平，实现抗 炎效果，并促进细胞增殖和血管生成，提高感染伤 口的闭合率。 Zhang 等 [79] 基于 Fe-Cu-N6 单原子纳米 酶制备的缝合线也能够促进血管内皮生长因子的分 泌，加速由脑外伤引起的头皮创伤的愈合。 糖尿病等慢性炎症疾病往往受高氧化应激水平 的影响，会引起伤口愈合速度变慢，因此开发能用 于糖尿病模型伤口愈合的纳米酶具有重要意义。Liu 等 [86] 利用 Cu5.4O USNPs 多重类酶活性， 将其成功应 用于糖尿病引起的伤口损伤的治疗中(图 5(g, i))。 作者发现，经 Cu5.4O USNPs 给药后 15 天小鼠伤口 达到 80%的愈合率(图 5(h, j)) 。经 Cu5.4O USNPs 给 药组的表皮再生长度和肉芽组织厚度均显著大于对 照组(图 5(k-n))， 说明 Cu5.4O USNPs 能够加速糖 尿病伤口愈合过程。Peng 等 [100] 将 Cu5.4O 超小纳米 酶负载于功能化的星形聚乙二醇(starPEG)和肝素 中得到复合水凝胶(Cu5.4O@Hep-PEG) ，该水凝胶 能够在伤口部位释放 Cu5.4O 超小纳米酶，清除伤口 部位过量的 ROS，促进急性伤口和糖尿病伤口的愈 合。 Fig. 5 Cu-based nanozymes for wound healing [86,98] (a) Schematic illustration of the Ni4Cu2 /F127 composite hydrogel dressing in wound healing; (b) Photographs of wounds with different treatments on days 0, 1, 3, 5, and 7 with scale bar representing 5 mm.…”

Mineral-Enhanced Manganese Ferrite with Multiple Enzyme-Mimicking Activities for Visual Detection of Disease Markers

“…Recently, enormous efforts have been made to develop inorganic nanostructured enzyme mimics (or nanozymes) for biosensing. − Unlike natural enzymes, nanozymes stand out due to their excellent stability, facile production, and easy storage, making them highly promising for diagnosing disease markers. − In this field, one of the bottlenecks is the limited catalytic efficiency of the enzyme mimics, a key parameter that determines the rate of signal generation and the strength of the detection signal . Among enzyme mimics, spinel oxides (AB 2 O 4 ) have a well-defined but tunable crystal structure with two sites, octahedral (Oh) and tetrahedral (Td) sites, and the distribution of cations in two sites determines its catalytic efficiency. − In general, the Oh sites play a primary role during the catalytic reaction because they are preferentially exposed on the near-surface, and a shorter distance between Oh–Oh sites accelerates the reaction kinetics. − Currently, most studies were primarily focused on modulating Oh metal ion species and valence states to enhance their catalytic efficiency.…”

Nanozyme-catalyzed cascade reaction enables a highly sensitive detection of live bacteria

“…To address these problems and widen the practical applications in harsh environments, nanozyme appears as a new emerging field instead of natural enzymes, [17][18][19][20][21] which possesses enzyme-like activity with high stability and tunable catalytic performances. [22][23][24][25] In a recent study, a 2D MOF-based nanozyme was used for the sensitive detection of bacteria coupled with an electrochemical detection technique. 10 Owing to the super stability of nanozyme, the present sensor exhibits good repeatability and high sensitivity towards bacterial detection.…”