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MICROCHIMICA ACTA · 2019 ·Vol. 187 ·期 1 ·1-8 · IF 5.479

Using zinc ion-enhanced fluorescence of sulfur quantum dots to improve the detection of the zinc(II)-binding antifungal drug clioquinol

Zhao Jie,Fan Zhefeng

A turn on–off fluorometric assay for clioquinol (CQ) is described here. It is based on modulation of the fluorescence of sulfur quantum dots (SQDs; best measured at excitation/emission wavelengths of 360/426 nm) by using the Zn 2+ -CQ affinity pair. Although the fluorescence enhancement effect of Zn 2+ on SQDs was not obvious, a good quenching modulation effect was observed in the presence of CQ. This resulted in a linear analytical range that is increased by two orders of magnitude (from 0.024 μM to 0.24 μM, and 0.62 μM to 30 μM), with a detection limit (3  s ) of 0.015 μM. The selectivity of the method is also improved. Schematic illustration of the turn on-off fluorometric assay for for clioquinol (CQ) based on Zn 2+ -modulated sulfur quantum dots (SQDs).

研究领域: 分析化学 · 药理学 · 生物医学工程
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JOURNAL OF HAZARDOUS MATERIALS · 2023 · IF 13.6

Fe(VI) activation system mediated by a solar-driven TiO2 nanotubes electrode for CLQ degradation: Performances, mechanisms and pathways

Jinzhe Li,Chuyun Fu,Qiufeng Lin,Tao Zeng,Da Wang,Xinwen Huang,Shuang Song,Cong Li,Feilong Dong

Ferrate (Fe(VI), FeO 4 2- ) has been widely used in the degradation of micropollutants with the advantages of high redox potential , no secondary pollution and inhibition of disinfection byproducts . However, the low transformation of Fe(V) and/or Fe(IV) by Fe(VI) and incomplete mineralization of pollutants limit their application. In this work, we designed a photo electric cell with TiO 2 nanotubes (TNTs) and Pt serving as the anode and cathode to enhance the utilization of Fe(VI) (Fe(VI)-TNTs system). TNTs accelerated the generation of •OH via h VB + oxidation of OH - and photogenerated electrons at Pt boosted the transformation of Fe(VI) to Fe(V) and/or Fe(IV), resulting in a 22.2 % enhancement of chloroquine (CLQ) removal compared to Fe(VI) alone. The results from EPR and quenching tests showed that Fe(VI), Fe(V), Fe(IV), •OH, O 2 •- and h VB + coexisted in the Fe(VI)-TNTs system, among which Fe(V) and Fe(IV) were testified as the primary reactive substances accounting for 59 % of CLQ removal. The performance tests and recycling tests demonstrated that the Fe(VI)-TNTs system maintained excellent performance in an authentic water environment. The plausible degradation pathway of CLQ oxidized in the Fe(VI)-TNTs system was proposed with nine identified oxidation products via N-C cleavage, electrophilic addition and carboxylation processes. Based on the ECOSAR calculation, the constructed reaction system allowed a decrease in acute and chronic toxicity. Our findings provide a highly efficient and cost-effective strategy to enhance Fe(VI) application for micropollutant degradation in the future.

研究领域: 环境科学 · 化学工程 · 材料科学
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Scientific Reports · 2021 ·Vol. 11 ·期 1 ·1-7 · IF 4.38

Development of a chiral HPLC method for the separation and quantification of hydroxychloroquine enantiomers

Xiong Xisheng,Wang Kun,Tang Tao,Fang Jinzhi,Chen Yijun

Hydroxychloroquine (2-[[4-[(7-Chloroquinolin-4-yl) amino]pentyl](ethyl) amino]-ethanol, HCQ), an effective anti-malarial drug, has been tested in the clinics for potential treatment of severe coronavirus disease 2019 (COVID-19). Despite the controversy around the clinical benefits of HCQ, the existence of a chiral center in the molecule to possess two optical isomers suggests that there might be an enantiomeric difference on the treatment of COVID-19. Due to their poor resolution and the inability of quantification by previously reported methods for the analysis of HCQ enantiomers, it is necessary to develop an analytical method to achieve baseline separation for quantitative and accurate determination of the enantiomeric purity in order to compare the efficacy and toxicity profiles of different enantiomers. In this study, we developed and validated an accurate and reproducible normal phase chiral high-performance liquid chromatography (HPLC) method for the analysis of two enantiomers of HCQ, and the method was further evaluated with biological samples. With this newly developed method, the relative standard deviations of all analytes were lower than 5%, and the limits of quantification were 0.27 μg/ml, 0.34 μg/ml and 0.20 μg/ml for racemate, R- and S-enantiomer, respectively. The present method provides an essential analytical tool for preclinical and clinical evaluation of HCQ enantiomers for potential treatment of COVID-19.

CAS / MDL: 110-54-3
研究领域: 药物化学 · 分析化学 · 传染病学
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COLLOIDS AND SURFACES B-BIOINTERFACES · 2024 · IF 5.4

Drug-induced self-assembled nanovesicles for chloroquine to sensitize MDR tumors to mitoxantrone hydrochloride

Juan Wang,Xinchen Zhao,Liyan Qiu

Multidrug resistance (MDR) is an incidental trouble post-chemotherapy, necessitating innovative therapeutic strategies. This study explores the potential of chloroquine (CQ) as a sensitizer for mitoxantrone hydrochloride (MitH) in drug-resistant tumors and introduces a novel pH-responsive drug-induced self-assembly nanovesicle (DIV) based on an amphiphilic polyphosphonitrile (PPAP) for the co-delivery of MitH and CQ. PPAP cannot self-assemble into nanovesicles alone, but when a certain amount of MitH was added, the multiple non-covalent interactions between PPAP and MitH contributed to the formation of DIV, which exactly improved the co-loading content of MitH and CQ to a large extent. CQ prevents MitH efflux and autophagy to reverse MitH resistance. Given the synergy between MitH and CQ at a 1:2 mass ratio with a combination index of 0.40 in K562/ADR cells, MitH and CQ co-loaded DIV (MC-DIV) is constructed and demonstrates a sensitivity index of 7.1 on cytotoxicity compared to free MitH. Furthermore, MC-DIV achieves extended circulation time, synchronous dual-drug delivery, and improved tumor targeting following systemic administration, resulting in exceptional antitumor efficacy in K562/ADR xenograft models with a tumor inhibition rate of 83.0 %. Overall, MC-DIV provides a viable method to maximize the loading capacity of nanocarriers, and potentially serves as a promising formulation for various MitH-resistant tumors.

研究领域: 药学 · 肿瘤学 · 纳米医学
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SENSORS AND ACTUATORS B-CHEMICAL · 2017 · IF 5.401

Ratiometric imaging of mitochondrial pH in living cells with a colorimetric fluorescent probe based on fluorescein derivative

Guli Li,Bei Zhang,Xinbo Song,Ying Xia,Haibo Yu,Xinfu Zhang,Yi Xiao,Youtao Song

Mitochondrial pH plays a pivotal role in the regulation of physiological process. Developing ratiometric fluorescent probes for real-time detection of mitochondrial pH fluctuation is still highly demanded yet challenging. Herein, we present a novel strategy to design a ratiometric probe (FDI) by broadening absorption spectrum (360–700   nm) of fluorescein fluorophore. Unsaturated dialkene/indole quaternary ammonium moiety has broadened absorption and emission spectrum of fluorescein fluorophore to provide ratiometric detection by CLSM in dual excitation/dual emission mode, as well as directionally accumulated in mitochondria in living cells. Superior to commercially mitochondrial tracker, Carboxy-SNARF, probe FDI exhibits excellent and fast cell-membrane permeability and mitochondrial-targetability. It has been demonstrated that FDI could permit real-time monitoring of pH alkalization of mitochondria stimulated by chloroquine. Owing to nondestructive process and reversible ratiometric response to pH, image acquisition can be repeated frequently to trace and monitor the time course of mitochondrial pH responses. It is clearly confirmed that FDI would be a promising probe for real-time tracking of mitochondrial pH changes in the biomedical and biological fields.

CAS / MDL: 2321-07-5
研究领域: 生物化学 · 细胞生物学 · 医学影像学
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SEPARATION AND PURIFICATION TECHNOLOGY · 2022 · IF 9.136

Nitrogen-rich based conjugated microporous polymers for highly efficient adsorption and removal of COVID-19 antiviral drug chloroquine phosphate from environmental waters

Xiao-Xing Wang,Lu Liu,Qi-Feng Li,Hua Xiao,Ming-Lin Wang,Hai-Chen Tu,Jin-Ming Lin,Ru-Song Zhao

Chloroquine phosphate (CQP) has been suggested as an important and effective clinical reliever medication for the 2019 coronavirus (COVID-19). Nevertheless, its excessive use will inevitably cause irreparable damage to the entire ecosystem, thereby posing a considerable environmental safety concern. Hence, the development of highly-efficient methods of removing CQP from water pollution sources, e.g., effluents from hospitals and pharmaceutical factories is significant. This study reported the fabrication of novel C N bond linked conjugated microporous polymers (CMPs) (BPT–DMB–CMP) with multiple nitrogen-rich anchoring sites for the quick and efficient removal of CQP from aqueous solutions. The irreversible covalent C N bond linked in the internal framework of BPT–DMB–CMP endowed it with good chemical stability and excellent adsorbent regeneration. With its predesigned functional groups ( i.e., rich N H bonds, triazine rings, and benzene rings) and large area surface (1,019.89 m 2 ·g −1 ), BPT–DMB–CMP demonstrated rapid adsorption kinetics (25 min) and an extraordinary adsorption capacity (334.70 mg·g −1 ) for CQP, which is relatively higher than that of other adsorbents. The adsorption behavior of CQP on BPT–DMB–CMP corresponded with Liu model and mixed-order model. Based on the density functional theory (DFT) calculations, X-ray photoelectron spectroscopy (XPS), and adsorption comparisons test, the halogen bonding, and hydrogen bonding cooperates with π − π, C   H···π interactions and size-matching effect in the CQP adsorption system on BPT–DMB–CMP. The excellent practicability for the removal of CQP from real wastewater samples verified the prospect of practical application of BPT–DMB–CMP. BPT–DMB–CMP exhibited the application potentials for the adsorption of other antiviral drugs. This work opens up an efficient, simple, and high adsorption capacity way for removal CQP.

研究领域: 环境科学 · 材料科学 · 公共卫生
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SEPARATION AND PURIFICATION TECHNOLOGY · 2024 · IF 8.1

Efficient adsorption of hydroxychloroquine by carboxylated lignin-based sponge: Quantification of the adsorption contribution of interactions

Boqiang Gao,Haoge Liang,Jie Wang,Yan Huang,Jingzhen Wang,Jia Song,Pan Hu,Hu Yang,Shuanglong Ma

Hydroxychloroquine (HCQ) as an antiviral pharmaceutical has been widely detected in the aquatic environment. Adsorption is an effective method for removal of HCQ, but the quantitative study of the adsorption interactions is unclear. In this study, a carboxylated lignin-based sponge (PLC) was fabricated, and the adsorption contributions of electrostatic attraction (EA), hydrogen bond (HB), and π-π electron donor–acceptor (π-π EDA) interactions were quantitatively investigated. The results showed that PLC exhibited excellent adsorption performance under wide pH range (4.0 < pH < 11.0), with the highest adsorption capacity of 0.165 mmol/g. Inhibitor and molecular probe experiments showed that EA and HB were the main contributors to adsorption at neutral and basic pH ranges, respectively. A linear correlation model of the carboxyl groups of lignin-based sponges with the adsorption capacity of EA, HB, and π-π EDA interactions of HCQ ( R 2  > 0.822) and three molecular probes ( R 2  > 0.749) was established, respectively. The optimal adsorption capacity was achieved by the synergistic combination of the deprotonated carboxyl of PLC with the HB of Ka1 amino, EA of Ka2 amino, and the π-π EDA of the quinoline ring. This study provided a new strategy for the quantitative construction of structure–activity relationships of adsorbents.

研究领域: 环境科学 · 材料科学 · 药学
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Nature Communications · 2025 ·Vol. 16 ·期 1 ·1-15 · IF 15.7

Structure-guided design of endosomolytic chloroquine-like lipid nanoparticles for mRNA delivery and genome editing

Liu Zhen,Wu Jiacai,Wang Ning,Lin Yongqi,Song Ruiteng,Zhang Min,Li Bin

Despite remarkable progress in designing RNA delivery systems, endosomal escape remains a recognized challenge for efficient RNA delivery. In this study, we develop a robust mRNA delivery platform termed endosomolytic chloroquine-like optimized lipid nanoparticles (ecoLNPs) for versatile mRNA delivery in vitro and in vivo via integrating the signature scaffold extracted from endosomolytic chloroquine into ionizable lipids. RNase-resistant ecoLNPs are capable of delivering a broad variety of mRNA payloads to diverse cell types, even hard-to-transfect 3D cells, with an efficiency of up to 18.9-fold higher than that of commercial transfection reagents. The pH-responsive endosomolytic activity of ecoLNPs can be largely attributed to the proton sponge effect and saposin B-promoted membrane disruption. In vivo, ecoLNPs enable potent local and systemic mRNA delivery and exhibit comparable potency to the clinically approved mRNA vaccine carrier, but strong tropism for lymph nodes following intramuscular injection. Furthermore, ecoLNPs are able to retain in vivo delivery potency for at least one week under non-frozen conditions and induce efficient genome editing in transgenic mice. Overall, the structure-guided integration strategy provides a pathway for de novo design of endosomolytic mRNA delivery systems.

CAS / MDL: 1154-25-2
研究领域: 分子生物学 · 纳米医学 · 药物递送
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Journal of Natural Medicines · 2024 · IF 2.5

Betulinic acid induces apoptosis of HeLa cells via ROS-dependent ER stress and autophagy in vitro and in vivo

Chen Ping,Zhang Xueer,Fang Qiaomiao,Zhao Zhongxiang,Lin Chaozhan,Zhou Yuan,Liu Fangle,Zhu Chenchen,Wu Aizhi

Betulinic acid (BA), a naturally occurring lupane-type triterpenoid, possesses a wide range of potential activities against different types of cancer. However, the molecular mechanisms involved in anti-cervical cancer about BA were rarely investigated. Herein, the role of BA in cervical cancer suppression by ROS-mediated endoplasmic reticulum stress (ERS) and autophagy was deeply discussed. The findings revealed that BA activated Keap1/Nrf2 pathway and triggered mitochondria-dependent apoptosis due to ROS production. Furthermore, BA increased the intracellular Ca 2+ levels, inhibited the expression of Beclin1 and promoted the expression of GRP78, LC3-II, and p62 associated with ERS and autophagy. Besides, BA initiated the formation of autophagosomes and inhibited autophagic flux by the co-administration of BA with 3-methyladenine (3-MA) and chloroquine (CQ), respectively. The in vivo experiment manifested that hydroxychloroquine (HCQ) enhanced the apoptosis induced by BA. For the first time, we demonstrated that BA could initiate early autophagy, inhibit autophagy flux, and induce protective autophagy in HeLa cells. Thus, BA could be a potential chemotherapy drug for cervical cancer, and inhibition of autophagy could enhance the anti-tumor effect of BA. However, the interactions of signaling factors between ERS-mediated and autophagy-mediated apoptosis deserve further attention. Graphical abstract

CAS / MDL: 118-42-3
研究领域: 肿瘤学 · 细胞生物学 · 药理学
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Catalysts · 2023 ·Vol. 13 ·期 4 ·661 · IF 3.9

Activation of Peroxymonosulfate Using Spent Li-Ion Batteries for the Efficient Degradation of Chloroquine Phosphate

Zhenzhong Hu,Jia Luo,Sheng Xu,Peng Yuan,Shengqi Guo,Xuejing Tang,Boxiong Shen

Recycling and reusing spent lithium-ion batteries (LIBs) have gained a lot of attention in recent years, both ecologically and commercially. The carbon nanotube-loaded CoFe2O4(CoFe2O4@CNTs) composite was made using a solvothermal technique utilizing wasted LIBs as the starting material and carbon nanotubes as support, and it was used as an efficient peroxymonosulfate (PMS, HSO5−) activator to degrade chloroquine phosphate (CQP). Scanning electron microscopy (SEM), transmission electron microscopy (TEM), an energy dispersive spectrometer (EDS), X-ray diffraction (XRD), Brunauer–Emmett–Teller (BET), and X-ray photoelectron spectroscopy (XPS) were utilized to characterize the physical and chemical properties of the catalyst generated. The impacts of CoFe2O4@CNTs dosage, PMS concentration, reaction temperature, initial pH value, starting CQP concentration, and co-existing ions have undergone extensive experimental testing. In comparison to bare CoFe2O4, the CoFe2O4@CNTs demonstrated increased catalytic activity, which might be attributed to their super electron transport capacity and large surface area. In ideal conditions, the mineralization efficiency and removal efficiency of 10 mg/L CQP approached 33 and 98.7%, respectively. By employing external magnets, the CoFe2O4@CNTs catalyst may be simply recycled and reused several times. The potential reaction mechanism in the CoFe2O4@CNTs/PMS system was also investigated. In summary, this study indicates that CoFe2O4@CNTs generated from spent lithium-ion batteries have a high potential in PMS activation for CQP and other pollutant degradation.Keywords:spent lithium-ion batteries;peroxymonosulfate activation;CoFe2O4@CNTs;chloroquine phosphate;recycle

CAS / MDL: 67-56-1 28752-68-3
研究领域: 环境科学 · 材料科学 · 化学工程
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BIOMATERIALS · 2017 · IF 8.402

Autophagy inhibition enabled efficient photothermal therapy at a mild temperature

Zhengjie Zhou,Yang Yan,Kewen Hu,Yuan Zou,Yiwen Li,Rui Ma,Qiang Zhang,Yiyun Cheng

The heterogeneously-distributed hyperthermia in nanomaterial-mediated photothermal therapy commonly results in incomplete tumor eradication and serious damage of health tissue. Here, we found autophagy was activated in cancer cells underwent photothermal therapy and the inhibition of autophagy significantly enhanced the efficacy of photothermal killing of cancer cells. A formulation of chloroquine-loaded polydopamine nanoparticles was developed for sensitized photothermal cancer therapy, and the in vitro and in vivo study demonstrated that inhibition of autophagy remarkably augmented the efficacy of photothermal therapy, leading to efficient tumor suppression at a mild temperature. The regulation of autophagy provides a new route to increase the efficacy of photothermal cancer therapy.

研究领域: 癌症研究 · 纳米技术 · 治疗学
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Journal of Environmental Chemical Engineering · 2023 · IF 7.7

Controllable synthesis of nanorod nickel doped cobalt molybdate as an efficient heterogeneous catalyst of peroxymonosulfate for degradation of chloroquine phosphate

Guosheng Zhang,Huiwen Ding,Jianqiao Wang,Pengfei Xiao

This study reports the preparation of an affordable Ni-doped CoMoO 4 catalyst (Ni X Co 1−X MoO 4 (X = 0–1)) via a hydrothermal method by substituting Co with Ni and investigated the performance and mechanism of Ni X Co 1−X MoO 4 catalyzing peroxymonosulfate (PMS) to degrade organic pollutants for the first time. Based on characterization, it can be observed that the synthesized Ni 0.5 Co 0.5 MoO 4 catalyst exhibited excellent surface properties and structural stability. Under optimal conditions, Ni 0.5 Co 0.5 MoO 4 and PMS synergistically achieved over 95% degradation of chloroquine phosphate (CQP) within 20 min, demonstrating superior performance. The degradation system maintained high efficiency under interference different interfering substances in aqueous media, exhibiting excellent tolerance and practicality. Elemental analysis and mechanistic studies of the catalyst showed that Ni doping promoted the reduction between Co 2+ /Co 3+ and Mo 4+ /Mo 6+ , which is critical for catalyst durability and reusability. The quenching experiment and electron paramagnetic resonance (EPR) show that the 1 O 2 generated through non-free radical pathways represented the predominant reactive species. A total of 19 intermediates were detected by LC-MS during degradation and possible pathways for CQP degradation were proposed and toxicity evaluation. After 5 cycles, the catalyst still showed good stability. Ni 0.5 Co 0.5 MoO 4 challenges including poor activation, metal ion leaching and low recovery of transition metal catalysts were addressed. This work offers new insights for the design of atom-doped spinel catalysts for catalytic oxidation and mechanism research. The Ni 0.5 Co 0.5 MoO 4 /PMS catalytic system can be extended to the treatment of other organic pollutants and even applied in the processing of high-concentration organic wastewater that requires rapid treatment, offering broader prospects for practical applications.

研究领域: 环境科学 · 催化化学 · 材料科学
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