Ziwei Zhang

The abnormally high expression of glutathione (GSH) in hepatocellular carcinoma (HCC) cells significantly contributes to chemotherapy resistance by neutralizing reactive oxygen species (ROS). To address this problem, we developed a nanocomposite probe (micelle@PDA@MnO₂ NPs) which was composed of free radical-labeled micelles as the core, polydopamine (PDA) as the inner shell and MnO₂ nanosheets as the outer shell. In the HCC microenvironment, the over-expressed GSH triggered the decomposition of the MnO₂ shell, releasing Mn²⁺ ions, and subsequently, the acidic condition and over-expressed carboxylesterase 2 (CES2) worked together to mediate the controlled release of nitroxide free radicals (i.e., TEMPONE) from the micelle core. With the help of dual-signal electron spin resonance (ESR) detection, it was found that much more free radicals and Mn²⁺ were released in hepatoma cells than in normal liver cells, rendering the proposed nanotherapeutic platform specific to HCC and a good candidate for free radical therapy and chemodynamic therapy (CDT). Moreover, the therapy featured an intelligent self-amplified property: the abundant GSH in the tumor microenvironment rapidly activated the decomposition of the nanocomposite and triggered the release of free radical TEMPONE and Mn²⁺, and TEMPONE and Mn²⁺ further amplified the oxidative stress to induce tumor apoptosis via ROS generation and GSH depletion. Finally, in combination with three therapy modes (Mn²⁺-mediated CDT, the oxidative stress enhancement effect of TEMPONE, and PDA-based photothermal therapy), significant therapeutic effects including facilitation of HepG2 cell apoptosis and inhibition of tumor growth in the HCC mouse model were achieved.

A highly sensitive aptamer sensor (aptasensor) is proposed based on metal–organic frameworks-silver nanoparticles (AgNPs@MOF) to detect sulfadimethoxine (SDM) by surface-enhanced Raman spectroscopy (SERS). AgNPs@MOF with SERS activity was successfully fabricated by synthesizing AgNPs in situ on the surface of MIL-101(Fe), and SDM aptamer and Raman reporter 4-aminophenthiophenol (4-ATP) were selected as specific recognition elements and signal probes, respectively. When SDM was absent, the SDM aptamers were effectively adsorbed on the surface of AgNPs@MOF, thus keeping AgNPs@MOF in a dispersed state, resulting in a weakened SERS signal of 4-ATP. In the presence of SDM, the combination of SDM and aptamer formed a rigid hairpin SDM-aptamer complex, which bound less to AgNPs@MOF. Therefore, fewer aptamers were adsorbed on AgNPs@MOF, which exposed more hot spots, resulting in an enhanced SERS signal of 4-ATP. The aptasensor had good selectivity and sensitivity towards SDM and a good linear relationship between SERS intensity and SDM concentration in the range 6.00–150.00 ng/mL, with the limit of detection as low as 2.73 ng/mL. Further application to honey and chicken samples spiked with SDM resulted in satisfactory recoveries, and the aptasensor showed good stability and reproducibility in real samples. The aptasensor based on AgNPs@MOF was proposed for the first time to detect trace SDM by SERS, which provided a favorable way to develop various sensing platforms for antibiotic detection in food safety. Graphical Abstract

Alkaline phosphatase (ALP) is an indispensable hydrolase in living organisms and the abnormality of ALP activity is correlated with a variety of diseases. Exploring ALP activity is important for clinical diagnosis and biomedical research to understand its physiological function. In this study, a dual-mode biosensing platform was constructed based on Cu-based metal–organic frameworks (Cu-MOFs) for electron spin resonance (ESR) and ultraviolet-visible (UV-vis) sensing of ALP. Cu-MOFs, as peroxidase mimics, catalyzed the decomposition of hydrogen peroxide (H₂O₂) and the generation of reactive oxygen species (ROS) which could oxidize ABTS into ABTS˙⁺ with good ESR and UV-vis signals. Pyrophosphate ions (PPi) with high affinity to Cu²⁺ in Cu-MOFs could suppress the peroxidase-like activity of Cu-MOFs, and ALP could hydrolyze PPi, resulting in the recovery of Cu-MOF catalytic activity. Thus, a quantitative dual-mode method for detection of ALP activity was established with good linearity in the range of 0–42 U L⁻¹ and limits of detection as low as 0.386 and 0.523 U L⁻¹ respectively for ESR and UV-vis detection. Benefiting from its high sensitivity and excellent selectivity, this method was applied for ALP detection in human serum and satisfactory recoveries were achieved. The off-on dual-mode sensing platform is more reliable than the single-mode sensor and shows merits like simple operation and cost-friendliness, making it have great potential in the diagnosis of ALP-related diseases.

Mn(II)-based electron spin resonance (ESR) spectroscopy was used for detecting butyrylcholinesterase (BChE) and organophosphorus pesticides (OPs). MnO₂ nanosheets were synthesized with manganese chloride and hydrogen peroxide. With the catalysis of BChE, S-butyrylthiocholine iodide (BTCh) was hydrolyzed into thiocholine which has a reducing -SH group. In the presence of thiocholine, MnO₂ nanosheets were broken down and Mn(IV) in MnO₂ nanosheets was reduced into Mn(II). Mn²⁺ is a paramagnetic ion and gives a good ESR signal. In contrast, MnO₂ nanosheets have no ESR signal and need not be separated from Mn²⁺. Mn²⁺ can be determined directly by ESR spectroscopy, and no further sensing probe is needed. ESR spectroscopy based on directly detecting Mn²⁺ is much simpler than those using other probes besides MnO₂. The ESR signal of Mn²⁺ is proportional to the catalytic activity of BChE. OPs which inhibit the activity of BChE can also be detected by probing the ESR signal of Mn²⁺. Since there is no ESR signal of MnO₂ nanosheets, the background signal in the absence of BChE was close to zero. The limit of detection (LOD) of BChE was as low as 0.042 U L^-1. The standard curve for determining the OP paraoxon was established by measuring the inhibition of BChE by paraoxon, and the LOD of paraoxon was found to be 0.076 ng mL^-1. The spiked Chinese cabbage extract samples were analyzed, and the experimental results indicated that the recoveries were from 96.5 to 102.8%. The planted Chinese cabbage was sprayed with the paraoxon solution, and the residue amount of paraoxon in the extract was estimated by the method. The result obtained by the present method was consistent with that obtained by HPLC, which proved the practicability of this new method.

The antioxidant capacity of 22 kinds of fruits was measured by the developed electron spin resonance (ESR) method based on Cu2+ sensor. Cu2+ is reduced to Cu+ by the antioxidants in the fruits, and the remaining Cu2+ was determined by ESR and UV-Vis spectroscopy. Cu2+ can give an ESR signal whereas Cu+ cannot, and the loss of the ESR signal was used to quantify the antioxidant capacity of various fruits. The results were shown as vitamin C equivalent antioxidant capacity (VCEAC). The VCEAC values obtained by ESR and UV-Vis methods ranged from 24.23 to 688.61 mg/100 g and from 24.12 to 677.79 mg/100 g, respectively. Cupric ion reducing antioxidant capacity (CUPRAC) and 1,1-diphenyl-2-picryl-hydrazyl (DPPH) methods were employed for comparison. Based on Pearson's correlation test, the results obtained by CUPRAC and DPPH methods were both significantly correlated with these obtained by the present method, which indicated that the novel method was reliable. Total phenolic content for all kinds of fruits was measured with the Folin-Ciocalteu reagent, and VCEAC values obtained by the ESR method were significantly correlated with total phenolic contents.