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Advanced Healthcare Materials · 2013 ·Vol. 3 ·期 2 ·261-272 · IF 0

Doxorubicin Conjugate of Poly(Ethylene Glycol)-Block-Polyphosphoester for Cancer Therapy

Chun-Yang Sun,Shuang Dou,Jin-Zhi Du,Xian-Zhu Yang,Ya-Ping Li,Jun Wang

Polyphosphoesters with repeating phosphoester linkages in the backbone can be easily functionalized, are biodegradable and potentially biocompatible, and may be potential candidates as polymer carriers of drug conjugates. Here, the efficacy of a polyphosphoester drug conjugate as an anticancer agent in vivo is assessed for the first time. With controlled synthesis, doxorubicin conjugated to poly(ethylene glycol)- block -polyphosphoester (PPEH–DOX) via labile hydrazone bonds form spherical nanoparticles in aqueous solution with an average diameter of ≈60 nm. These nanoparticles are effectively internalized by MDA-MB-231 breast cancer cells and release the conjugated doxorubicin in response to the intracellular pH of endosomes and lysosomes, resulting in significant antiproliferative activity in cancer cells. Compared with free doxorubicin injection, PPEH–DOX injection exhibits much longer circulation behavior in the plasma of mice and leads to enhanced drug accumulation in tumor cells. In an MDA-MB-231 xenograft murine model, inhibition of tumor growth with systemic delivery of PPEH–DOX nanoparticles is more pronounced compared with free doxorubicin injection, suggesting the potential of polyphosphoesters as carriers of drug conjugates in cancer therapy.

CAS / MDL: 2935-90-2
研究领域: 药学 · 生物医学工程 · 癌症研究 · 聚合物科学
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BIOSENSORS & BIOELECTRONICS · 2016 · IF 7.476

Highly sensitive visual detection of Avian Influenza A (H7N9) virus based on the enzyme-induced metallization

Huifang Zhang,Xiaoming Ma,Shuisheng Hu,Yue Lin,Longhua Guo,Bin Qiu,Zhenyu Lin,Guonan Chen

Development of convenient but sensitive method for influenza detection is highly important in immediate and effective clinical treatment. In this study, an ultrasensitive colorimetric approach combining the advantages of the convenience of the enzyme-induced metallization and the high specificity of enzyme-linked immunosorbent assay for the detection of influenza virus A (H7N9 as model) has been developed. Two rounds of amplification are utilized to enhance the detection sensitivity. The amplification of enzymatic reaction combines with the specific optical properties of gold nanoparticles causing the enhancing of the optical signal immensely. In addition, the increased surface area and the magnetic enrichment effect also enable the magnetic bead (MB) to catch a large number of alkaline phosphatase (ALP) and detection antibody (Ab 2 ), thus very small amounts of the virus can be easily detected. Compared with conventional method, this approach exhibits outstanding sensitivity for ALP detection, 0.2   U/L of ALP can be distinguished with a spectrometer and 2   U/L with the naked eye. And as low as 25   pg/mL of H7N9 can be detected by the naked eye. This approach shows an extensive horizon for bioassays and is available in clinical diagnosis with the advances of simplification, effectiveness, low cost and sensitive readout.

研究领域: 病毒学 · 诊断医学 · 纳米技术 · 分析化学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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NANOTECHNOLOGY · 2022 ·Vol. 33 ·期 27 ·275604 · IF 3.953

pH-responsive and CD44-targeting polymer micelles based on CD44p-conjugated amphiphilic block copolymer PEG-b-HES-b-PLA for delivery of emodin to breast cancer cells

Kai Cheng,Jie Zhou,Yujie Zhao,Yu Chen,Lan Ming,Da Huang,Rui Yang,Zhenyu Lin,Daozhen Chen

Herein, an amphiphilic block copolymer CD44-targeting peptide-conjugated polyethylene glycol-block-hydroxyethyl starch-block-poly (L-lactic acid) (CD44p-conjugated PEG-b-HES-b-PLA) are synthesized, which could self-assemble into the pH-responsive and CD44-targeting polymer micelles against breast cancer cells MDA-MB-231. Emodin (Emo) is a natural anthraquino with pharmacological activities in anti-tumor effects. However, Emo suffers from poor water solubility, low biocompatibility, rapid systemic elimination, and off-target side effects, resulting in unsatisfactory treatment outcomes. Nanotechnology-based drug delivery systems have proven great potential for cancer chemotherapy. The constructed polymeric micelles Emo@CD44p-PM have exhibited an average size of 154.5 ± 0.9 nm characterized by DLS and TEM. Further, the Emo@CD44p-PM have effective Emo-loading capacity, good thermal stability, and pH responsiveness. Intracellular uptake study shows the enhanced cellular internalization of Emo@CD44p-PM due to the increased exposure of CD44p enhances the cellular internalization of Emo@CD44p-PM effectively. Furthermore, the in vitro results showed Emo@CD44p-PM has been observed good biocompatibility and anti-tumor effects. Therefore, the polymeric micelles Emo@CD44p-PM provide a promising delivery strategy of targeted therapy for breast cancer.

研究领域: 纳米技术 · 药学 · 癌症研究 · 高分子化学
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ANALYTICAL BIOCHEMISTRY · 2022 · IF 3.191

A novel ratiometric electrochemical aptasensor for highly sensitive detection of carcinoembryonic antigen

Ping Wang,Yaoyao Xie,Huikai Ma,Jiancheng Liu,Chenxiang Liu,Wei Feng,Shoumin Xi

A novel ratiometric electrochemical aptasensor was proposed for carcinoembryonic antigen (CEA) detection based on exonuclease III (Exo III)-assisted recycling and rolling circle amplification (RCA) strategies. A thiolated ferrocene-labeled hairpin probe 2 (Fc-HP2) was fixed on the gold nanoparticles (AuNPs)-modified gold electrode (AuE) surface through Au–S bonds. The presence of CEA led to the release of trigger, which hybridized with the 3′-protruding of hairpin probe 1 (HP1) and triggered the Exo III cleavage reaction, accompanied by the releasing of trigger and generation of new DNA fragment which was used for the successive hybridization with Fc-HP2. After the Exo III cleavage process, the remaining Fc-HP2 fragments hybridized as primers with the RCA template to initiate the RCA process, and long single-stranded polynucleotides were produced for methylene blue (MB) binding. Such changes resulted in the signal of Fc (I Fc ) decreased and that of MB (I MB ) increased, achieving a linear relationship between I MB /I Fc and logarithm of CEA concentrations ranging from 1.0 pg mL −1 to 100.0 ng mL −1 with a detection limit of 0.59 pg mL −1 . Additionally, the developed aptasensor had been successfully applied to detect CEA in human serum samples. Therefore, the proposed strategy might provide a new platform for clinical detections of CEA.

研究领域: 生物化学 · 分析化学 · 生物医学工程
✓ 已验证 DOI PubMed 高影响因子
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Desalination and Water Treatment · 2024 · IF 1

Efficient removal of toxic methylene blue (MB) dye from aqueous solution using a metal-organic framework (MOF) MIL-101(Fe): isotherms, kinetics, and thermodynamic studies

Abdelazeem S. Eltaweil,Eman M. Abd El-Monaem,Ahmed M. Omer,Randa E. Khalifa,Mona M. Abd El-Latif,Gehan M. El-Subruiti

MIL-101(Fe) iron-benzene dicarboxylate based metal-organic framework (MOF) was synthesized via a solvothermal method for adsorptive removal of cationic methylene blue (MB) dye from aqueous solution. The prepared MIL-101(Fe) was characterized by X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, transmission electron microscopy, thermal gravimetric analyzer, X-ray photoelectron spectroscopy, and Brunauer–Emmett–Teller analysis tools. Various parameters affecting the removal efficiency were deliberated such as pH medium, contact time, solution temperature, MOF dosage, and initial MB dye concentrations. Results showed that MIL-101(Fe) has a maximum adsorption capacity of 58.82 mg/g at pH 9. Moreover, data obtained from isotherm studies were more fitted to the Langmuir isotherm model (R 2 = 0.997), while the adsorption kinetics followed the pseudo-second-order model. The thermodynamic studies proved that the adsorption process of MB dye onto MIL-101(Fe) was spontaneous and endothermic. Besides, MIL-101(Fe) showed higher adsorption ability towards cationic MB dye compared to the anionic methyl orange dye. Finally, the MIL-101(Fe) adsorbent showed excellent reusability for removing MB dye with efficiency exceeded 70% after ten consecutive cycles. Therefore, the as-prepared MIL- 101(Fe) could be applied as a reusable adsorbent for removing cationic dyes from their aqueous solutions.

研究领域: 环境科学 · 材料科学 · 化学工程 · 纳米技术 · 污染控制
✓ 已验证 DOI 高影响因子
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Environmental Science-Processes & Impacts · 2021 ·Vol. 23 ·期 5 ·735-744 · IF 4.238

A novel WH-flags method based on reducing the acidity of molybdenum blue (MB) reaction and stabilization by EDTA for quickly detecting phosphorus in water

Yanghui Xiong,Yuan-Bo Wang,De-Sheng Pei

There are two popular methods to measure reactive phosphorus (P) and total P: the GB11893-89 method in China and the 4500-P E method of the APHA in the US. However, their drawbacks, including long reaction time and narrow linear range, cannot satisfy the demand for modern analytic techniques. Here, based on reducing the acidity of the molybdenum blue (MB) reaction, and then stabilizing with EDTA, we have developed a novel method (WH-flags) to quickly measure both reactive P and total P. In the WH-flags method, “W” stands for Wide linear ranges (0–1.4 mg L−1 for reactive P & 0–1.8 mg L−1 for total P), “H” stands for High tolerance of different matrices (it can be adapted to a wide spectrum of samples), “f” is fast reaction time (2 min), “l” is long stabilization (40 min), “a” stands for appropriate recovery rates (89.1–103.2%), “g” is good precision and accuracy (CVs < 5% & Res < 5%) and “s” is small volume of samples (5–10 mL). The WH-flags method showed good linearity (R2 > 0.999). The WH-flags method should have broad application in monitoring P from different aqueous samples in the future.

研究领域: 环境科学 · 分析化学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF MEDICINAL CHEMISTRY · 2024 · IF 6.8

Target Ligand Separation and Identification of Isoforsythiaside as a Histone Lysine-Specific Demethylase 1 Covalent Inhibitor Against Breast Cancer Metastasis

Mengzhen Gu,Xiaoqing Xu,Xiaoping Wang,Yun Wang,Yu Zhao,Xiaoxian Hu,Lu Zhu,Zhenzhong Deng,Chao Han

Histone lysine-specific demethylase 1 (LSD1) is hyperactive in breast cancer, which is associated with the metastasis of the tumor. Current irreversible LSD1 inhibitors are all synthesized by covalently binding to the flavin adenine dinucleotide cofactor, which often have side effects due to the high affinity for a variety of targets. Here, we identified isoforsythiaside (IFA), a natural phenylpropanoid glycoside isolated from Forsythia suspensa, as a novel covalent inhibitor of LSD1. The target ligand fishing technique and LC–MS/MS analysis identified that IFA could covalently bind to the Ser817 residue of LSD1 by α,β-unsaturated ketone moiety to block the amine oxidase-like domain of LSD1. Moreover, RBMS3/Twist1/MMP2, the downstream signaling pathway of LSD1, was activated after IFA treatment to inhibit the metastasis of MDA-MB-231 cells in vitro and in vivo. This study provided novel molecular templates for development of LSD1 covalence-binding inhibitor and laid a foundation for developing agents against breast carcinoma metastasis for targeting LSD1.

CAS / MDL: 66-81-9
研究领域: 癌症生物学 · 药理学 · 分子生物学 · 生物化学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Journal of Materials Chemistry B · 2018 ·Vol. 6 ·期 12 ·1834-1843 · IF 4.776

Extracellular retention of a cyclopamine nanoformulation leveraging larger size and more negative charge for improved breast cancer treatment

Chan Feng,Kun Wang,Yun Lin,Zhiwang Song,Yonglin Lu,Jie Liu,Donglei Zhu,Yongyong Li,Chunyan Dong

Compared with intracellular drug delivery, drugs with extracellular targeting sites are rarely considered. As one of these drugs, cyclopamine (CYC) is a promising anticancer drug that functions by targeting the cell membrane receptor. For improving therapeutic effect, an albumin-based nano-system (ABN) with the capacity for extracellular retention was developed. The ABN was formulated by incorporating bovine serum albumin (BSA) into nanoparticles at the denaturing temperature of BSA, with CYC acting as a hydrophobic nucleation site, followed by stabilization upon heat-induced disulfide cross-linking. The resultant ABNs are negatively charged with a nanoparticle size that can be delicately regulated by varying the reaction time. In MDA-MB-231 cells, the size and charge of ABNs significantly affected the extracellular retention capacity, with ABN-300 nm exhibiting an enhanced cytotoxic effect. In vivo fluorescence imaging revealed obvious and persistent tumor accumulation of ABNs. A therapeutic study in an orthotopic mammary fat pad tumor model shows that ABN-300 nm possesses the most remarkable antitumor effect compared with the control groups. These results provide a new strategy for improving the efficacy of drug targeting at extracellular sites.

研究领域: 药学 · 纳米技术 · 肿瘤学 · 药物递送系统
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Acta Biomaterialia · 2017 · IF 6.319

Visible light-switched cytosol release of siRNA by amphiphilic fullerene derivative to enhance RNAi efficacy in vitro and in vivo

Jing Wang,Lifei Xie,Tao Wang,Fengxin Wu,Jie Meng,Jian Liu,Haiyan Xu

Cationic macromolecules are attractive for use as small interfering RNA (siRNA) carriers due to their performance in non-immunological reactions, customization during synthesis, and low costs compared to viral carriers. However, their low transfection efficiency substantially hinders their application in both clinical practices and academic research, which is mostly attributable to the low capacity of siRNA/cationic macromolecule complexes to escape lysosomes . To address this challenge, we designed an amphiphilic fullerene derivative (C 60 -Dex-NH 2 ) for efficient and controllable siRNA delivery. To synthesize C 60 -Dex-NH 2 , terminally aminated dextran was conjugated to C 60 . The conjugate was further cationized by covalently introducing ethylenediamine to the dextran. The physicochemical characteristics of C 60 -Dex-NH 2 was examined with elemental analyses, gel permeation chromatography , solid-state nuclear magnetic resonance ( 13 C, HPDEC), agarose gel electrophoresis , and dynamic light scattering . The cytotoxicity, cellular uptake, intracellular distribution , and in vitro RNA interference (RNAi) of siRNA/C 60 -Dex-NH 2 complex was evaluated in the human breast cancer cell line MDA-MB-231. The RNAi efficiencies mediated by C 60 -Dex-NH 2 in vivo was evaluated in subcutaneous tumor-bearing mice. The results showed that C 60 -Dex-NH 2 has a specific amphiphilic skeleton and could form micelle-like aggregate structures in water, which could prevent siRNA from destroying by reactive oxygen species (ROS). When exposed to visible light, C 60 -Dex-NH 2 could trigger controllable ROS generation which could destroy the lysosome membrane, promote the lysosomal escape, and enhance the gene silencing efficiency of siRNA in vitro and in vivo . The gene silencing efficiency could reach a maximum of 53% in the MDA-MB-231-EGFP cells and 69% in the 4T1-GFP-Luc2 tumor-bearing mice. Statement of Significance We designed a novel photosensitive amphiphilic carrier (C 60 -Dex-NH 2 ) for efficient and controllable siRNA delivery, which can be used in gene therapy. We showed that C 60 -Dex-NH 2 could destroy lysosome membrane via controllable generation of ROS when exposed to light, which can help siRNA to escape from lysosome before degradation. This can enhance the gene silencing efficiency significantly and provides a useful way to regulate RNAi efficiency by light. One advantage for C 60 -Dex-NH 2 system is C 60 has broad absorbance spectrum and can be activated by weak visible light; Furthermore, C 60 -Dex-NH 2 has a specific amphiphilic structure, which may prevent siRNA from degrading and allows C 60 -Dex-NH 2 to embed into the lipid membrane of lysosome to improve the ROS induced lysosomal disturbance after internalization .

研究领域: 药学 · 纳米技术 · 分子生物学 · 癌症研究
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Scientific Reports · 2023 ·Vol. 13 ·期 1 ·1-11 · IF 4.6

The enhanced cytotoxicity on breast cancer cells by Tanshinone I-induced photodynamic effect

Fengchao Chen,Siya Zhang,Tongtong Yan,Hongquan Wang,Jie Li,Qiang Wang,Danish Subhan,Kun Li

Recently, natural photosensitizers, such as berberine, curcumin, riboflavin, and emodin, have received more and more attention in photodynamic therapy. Tanshinone I (TanI) is extracted from a traditional Chinese herb Danshen, and exhibits many physiological functions including antitumor. TanI is a photoactive phytocompounds, but no work was tried to investigate its potential photodynamic effect. This study evaluated the cytotoxicity induced by the photodynamic effect of TanI. The photochemical reactions of TanI were firstly investigated by laser flash photolysis. Then breast cancer cell line MDA-MB-231 was chosen as a model and the photodynamic effect of TanI on cancer cell was evaluated by MTT assay and flow cytometry. The results showed that TanI could be photoexcited by its UV–Vis absorption light to produce 3 TanI* which was quickly quenched by O 2 . MTT assay showed that the photodynamic effect of TanI resulted in more obvious inhibitive effect on cell survival and cell migration. Besides, the photodynamic effect of TanI could induce cell apoptosis and necrosis, lead to cell cycle arrest in G2, increase intracellular ROS, and decrease the cellular Δψm. It can be concluded that the photodynamic effect of TanI can obviously enhance the cytotoxicity of TanI on MDA-MB-231 cells in vitro, which indicated that TanI might serve as a natural photosensitizer.

研究领域: 药理学 · 肿瘤学 · 光动力疗法 · 细胞生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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SENSORS AND ACTUATORS B-CHEMICAL · 2023 · IF 8.4

A high-sensitivity AuNPs/MWCNTs-MB/DNA-GCE quadruplex biosensor for Pb detection in medicinal teas through in-situ monitoring microstructure and conformational switch by SECM

Ming Sui,Yanni Huang,Yang Tang,Jiaoyang Luo,Yiyang Dong,Yifei Guo,Yonggui Ma,Wei Gu,Mengyue Guo,Jingdan Huang,Dandan Kong,Jinping Li,Meihua Yang

Medicinal teas (MT) were popular in Asian countries for its various effective components. However, Pb pollution poses a serious threat to MT consumption due to the irreversible effect on enzyme activity and neurodegenerative disease. Owing to its toxicity and matrix interference, a rapid screening method for Pb at trace level with high sensitivity and accuracy is urgent for MT consumers. Herein, a simple and ultra-sensitive AuNPs/MWCNTs-MB/DNA-GCE quadruplex biosensor was developed and investigated. Specifically, the monitoring technology of scanning electrochemical microscope was utilized to analyze the assembly and application process for screening key parameters in complex matrix , through in-situ characterization of the microstructure changes on stepwise modified sensors. According to the combined results of electrochemical test and Randles-Sevcik equation, the proposed sensor showed a wide linear range from 5.0 * 10 −15 to 5.0 * 10 −13 M with LOD of 0.9 fM. In addition, the optimized sensor exhibited an excellent selectivity under the inference of metals and medicinal components. The proposed biosensor was successfully implemented for the ultrasensitive monitoring Pb pollution in MT while its water infusions recoveries maintained within acceptable range (81–118 %, 82–129 %). In all, AuNPs/MWCNTs-MB/DNA-GCE provided a new insight into the design, optimization, application and mechanism analysis of sensor for reliable sensing in controlling MT pollution and consumption safety.

研究领域: 分析化学 · 环境科学 · 材料科学 · 生物技术
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ANALYTICA CHIMICA ACTA · 2020 · IF 5.977

A reusable neurotransmitter aptasensor for the sensitive detection of serotonin

Xue Geng,Mengtian Zhang,Hongyan Long,Ziheng Hu,Biying Zhao,Lingyan Feng,Jiangyan Du

Serotonin is one of the important neurotransmitters in human nervous system and associated with central nervous system diseases. Herein, we have prepared a novel electrochemical aptasensor for rapid and sensitive detection of serotonin by using the pre-designed and prepared DNA aptamers . In the absence of serotonin, the electron transfer rate on the aptasensor was faster than that in the presence of serotonin due to the hairpin structure of the aptamer was loose and MB could be closer to the electrode surface. While in the presence of serotonin, the hairpin structure of the aptamer was extended and MB was far away from the electrode surface. The effect of MB labeled sites on analytical performances of the proposed aptasensors was discussed by comparing sensitivity of the aptasensors that MB labeled in the intermediate of the aptamer with that MB labeled at the 3′ end of the aptamer. It was found that sensitivity of the intermediate-labeled aptasensor was much higher than the terminal-labeled aptasensor due to the specific conformational changes before and after aptamer binding to serotonin. The developed aptasensors exhibits a rapid electrochemical response and high sensitivity for the determination of serotonin. Under the optimal experimental conditions, the linear range for serotonin concentrations by the intermediate-labeled aptasensor was 1 pM–10 nM with a detection limit of 0.017 fM (S/N = 3). Moreover, the proposed aptasensor is reusable and shows good reproducibility and selectivity for the detection of serotonin in 100-fold diluted rat cerebrospinal fluid , suggesting a good application prospect in the detection of serotonin in real samples.

研究领域: 分析化学 · 神经科学 · 生物传感器 · 电化学
✓ 已验证 DOI PubMed 高影响因子
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