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SENSORS AND ACTUATORS B-CHEMICAL · 2017 · IF 5.401

Sensitive label-free resonance Rayleigh scattering DNA machine-based dual amplification strategy for the active uracil-DNA glycosylase assay

Xiao Fang Zhang,Na Li,Cui Ye,Jia Yu Liang,Nian Bing Li,Hong Qun Luo

Uracil-DNA glycosylase (UDG), one of the base-excision repair enzymes, is closely relevant for the diseases of the organism. Here, we proposed a resonance Rayleigh scattering (RRS) strategy for sensitively detecting the active UDG based on a dual amplification DNA machine without label under the catalysis of exonuclease III (Exo III). In our study, a double-stranded DNA complex S1-S2 containing triggers and peculiar uracil bases was employed. To achieve the dual amplification strategy, we adopted hairpin probes HP1 and HP2. The unique hairpin probes can partially hybridize with S1 and S2, respectively. With the excision reaction of UDG, the uracil bases were excised from S2 in double-stranded S1-S2, resulting in a lower melting temperature of the S1-S2. Then, the S1-S2 was dissociated to single-stranded S1 and S2 with abasic sites. Subsequently, the liberated strands separately hybridized with hairpins to initiate the Exo III-catalyzed dual amplification. In the presence of K + , countless c-myc sequences which were produced by the amplification reaction formed G-quadruplex structures. Finally, with the addition of Mg 2+ , long and continuous G-wire structures were obtained, causing an obvious enhancement of RRS intensity. The proposed RRS DNA machine obtained the limit of detection as low as 1.0   ×   10 −5   U/mL for the active UDG assay. Moreover, qualitative analysis of the active UDG was successfully achieved in HeLa cells lysate. The DNA machine is a potential tool to be used in UDG clinical diagnosis or functional study.

CAS / MDL: 77-86-1
研究领域: 分子生物学 · 分析化学 · 生物医学工程 · 临床诊断
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BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS · 2017 · IF 2.466

Mito-methyl coumarin, a novel mitochondria-targeted drug with great antitumor potential was synthesized

Huanan Wang,Wenqing Xu

Due to higher transmembrane potential of tumor cells, enhanced accumulation of cationic drugs in tumor mitochondria has been attributed to a higher (more negative inside) mitochondrial transmembrane potential compared with normal cells, emerging researchers are focus on developing mitochondria-targeted antitumor drugs. Coumarins showed great potential on antitumor, but mitochondria-targeted coumarin derivatives have not been reported. In the present study, we synthesized mitochondria-targeted-methyl coumarin (mito-methyl coumarin) through coupling 6-methyl coumarin to TPP. We confirmed that mito-methyl coumarin inhibited HeLa cells proliferation selectively, induced ROS generation, reduced mitochondrial membrane potential , promoted mitochondria Ca 2+ accumulation, decreased mitochondria mass and induced HeLa cells apoptosis, but methyl coumarin did not. These results demonstrate that we succeed in synthesizing a novel mitochondria-targeted drug, mito-methyl coumarin, which is effective in inhibiting HeLa cells proliferation and inducing HeLa cells apoptosis through promoting ROS generation and mitochondria Ca 2+ accumulation.

研究领域: 药理学 · 肿瘤学 · 细胞生物学
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Frontiers in Pharmacology · 2026 · IF 5.4

Crocus sativus L.-derived lauric acid-functionalized gold nanoparticles induce ferroptosis in HeLa cells and reverse M2 macrophage polarization via the PGE2/EP2/cAMP-PKA signaling pathway: a network pharmacology-based study

Jie Weng,Songlian Liu,Yajun Tong,Kewei Tang,Leilan Yin,Site Bai,Ludi Ou,Qinghua Yin,Qiang Zhou

Introduction Cervical cancer ranks as the fourth most common malignancy among women worldwide. It is closely associated with the dysregulation of numerous genes and signaling pathways. Conventional treatments for cervical cancer often lead to adverse side effects and the development of drug resistance. Methods In this study, network pharmacology was employed to identify the active components and potential targets of Crocus sativus L. Molecular docking and surface plasmon resonance analyses were used to validate the interaction between lauric acid and a key target. Lauric acid‐modified gold nanoparticles (Au@LA) were synthesized and characterized. Results Twenty‐three active components and 819 potential targets of Crocus sativus L. were identified, with PTGS2 being the main target. Au@LA selectively inhibited HeLa cell proliferation, induced apoptosis, downregulated SLC7A11 and GPX4, and modulated oxidative stress markers. In macrophages, Au@LA shifted M2 polarization to the pro‐inflammatory M1 phenotype and modulated the PGE2/EP2/cAMP‐PKA signaling axis. Conclusion Our findings indicate that Au@LA has dual anti‐cervical cancer properties through inducing ferroptosis in HeLa cells and reprogramming macrophage polarization. It shows promise as a candidate for natural product‐based nanomedicine in cervical cancer therapy, potentially opening new avenues for more effective and targeted treatments in the future.

CAS / MDL: 156-57-0
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MOLECULAR PHARMACEUTICS · 2020 · IF 4.321

Cell Type-Dependent Specificity and Anti-Inflammatory Effects of Charge-Reversible MSNs-COS-CMC for Targeted Drug Delivery in Cervical Carcinoma

Lan Cui,Xiayi Feng,Wentao Liu,Hao Liu,Qian Qin,Shuangxia Wu,Suqin He,Xinchang Pang,Dong Men,Chengshen Zhu

The surface charge of nanocarriers inevitably affects drug delivery efficiency; however, the cancer cell specificity, anti-inflammatory effects, and charge-reversal points remain to be further addressed in biomedical applications. The aim of this study was to comprehensively assess the cancer cell specificity of DOX-loaded mesoporous silica-chitosan oligosaccharide-carboxymethyl chitosan nanoparticles (DOX@MSNs-COS-CMC) in MCF-7 and HeLa cells, inhibit the production of inflammatory cytokines, and improve the drug accumulation in the tumor site. Intracellular results reveal that the retention time prolonged to 48 h in both HeLa and MCF-7 cells at pH 7.4. However, DOX@MSNs-COS-CMC exhibited a cell type-dependent cytotoxicity and enhanced intracellular uptake in HeLa cells at pH 6.5, due to the clathrin-mediated endocytosis and macropinocytosis in HeLa cells in comparison with the vesicular transport in MCF-7 cells. Moreover, Pearson’s correlation coefficient value significantly decreased to 0.25 after 8 h, prompting endosomal escape and drug delivery into the HeLa nucleus. After the treatment of MSNs-COS-CMC at 200 μg/mL, the inflammatory cytokines IL-6 and TNF-α level decreased by 70% and 80%, respectively. Tumor inhibition of DOX@MSNs-COS-CMC was 0.4 times higher than free DOX, alleviating cardiotoxicity and inflammation in the HeLa xenograft tumor model. Charge-reversible DOX@MSNs-COS-CMC could be a possible candidate for clinical therapy of cervical carcinoma.

研究领域: 药理学 · 肿瘤学 · 生物医学工程 · 纳米技术
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ANALYTICA CHIMICA ACTA · 2022 · IF 6.911

Highly efficient incorporation of dATP in terminal transferase polymerization forming the ploy (A)n-DITO-1 fluorescent probe sensing terminal transferase and T4 polynucleotide kinase activity

Jing Zhu,Liutao Chen

Fluorescent dye DITO-1 has almost no fluorescence in the absence of nucleic acid . G bases in single strand DNA can induce maximum fluorescent enhancement followed by the A bases when it binds the DITO-1. However, the incorporation efficiency of the dATP was higher than dGTP in terminal transferase (TdT) polymerization. As a consequence, ploy (A) n , rather than ploy (G) n via TdT polymerization had the superior photoluminance when it binded DITO-1 fluorescent dye. Here, we developed a high selective and sensitive sensing strategy for assaying TdT and T4 polynucleotide kinase activity (T4 PNK) based on the ploy (A) n -DITO-1 fluorescent probe. An increasing amounts of TdT enzyme could promote the distinct incorporation of dATP on the DNA primer and form poly (A) n ssDNA with a difference in length. A good linear relationship between the ΔF and the concentrations of TdT in a range of 0.2–50 U/mL was obtained and the detection limit was 0.05 U/mL. Based on the experimental results for TdT, we further expanded the application of this method for detection of a series of concentrations of T4 PNK. The ΔF and the logarithm concentrations of T4 PNK in the range of 0.1–10 U/mL showed a good linear response and the detection limit of 0.02 U/mL was obtained. In addition, the detection of T4 PNK in Hela cell lysate was achieved, demonstrating that the proposed method had the potential application in complex system. The ploy (A) n -DITO-1 fluorescent probe had the excellent properties of one-step readout, robustness for target detection in complex system, and easiness operation, and showed the great potential in clinical diagnostics, inhibitor screening, and drug discovery.

研究领域: 分子生物学 · 生物化学 · 分析化学 · 生物医学工程
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CHEMISTRY OF NATURAL COMPOUNDS · 2025 · IF 0.9

Synthesis and Cytotoxicity of New 1,2,3-Triazole Derivatives of Abietic Acid

Wang Yong,Wang Wei,Liu Li-Na,Wei Dong-Lin,Liu Cong-Jun,Wei Shang-Hua,Gao Song,Yu Shu-Ping,Yao Ning,Wang Yu-Fei

A series of abietic acid derivatives modified with a triazole moiety at the C-18 position were synthesized using Huisgen 1,3-dipolar cycloaddition reaction of 18-azidoabietane with alkynes. The antitumor activity of the synthesized compounds was investigated through human cervical cancer cells (HeLa), human breast cancer cells (MCF-7) and human renal epithelial cells (HEK-293T). The outcome indicated that compounds 5e , 5f , 5j exhibited positive inhibitory activity against the tested tumor cell lines. In particular, the IC 50 value for the inhibitory activity of compound 5e against human breast cancer cells (MCF-7) was 11.2 μmol/L.

研究领域: 药物化学 · 有机合成 · 肿瘤药理学 · 天然产物衍生物
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COLLOIDS AND SURFACES B-BIOINTERFACES · 2015 · IF 4.152

Baicalin loaded in folate-PEG modified liposomes for enhanced stability and tumor targeting

Yiyin Chen,Le Van Minh,Jianwen Liu,Borislav Angelov,Markus Drechsler,Vasil M. Garamus,Regine Willumeit-Römer,Aihua Zou

Bioavailability of baicalin (BAI), an example of traditional Chinese medicine, has been modified by loading into liposome. Several liposome systems of different composition i.e., lipid/cholesterol (L), long-circulating stealth liposome (L-PEG) and folate receptor (FR)—targeted liposome (L-FA) have been used as the drug carrier for BAI. The obtained liposomes were around 80   nm in diameter with proper zeta potentials about −25   mV and sufficient physical stability in 3 months. The entrapment efficiency and loading efficiency of BAI in the liposomes were 41.0–46.4% and 8.8–10.0%, respectively. The morphology details of BAI lipsosome systems i.e., formation of small unilamellar vesicles, have been determined by cryogenic transmission electron microscopy (cryo-TEM) and small angle X-ray scattering (SAXS). In vitro cytotoxicity of BAI liposomes against HeLa cells was evaluated by MTT assay. BAI loaded FR-targeted liposomes showed higher cytotoxicity and cellular uptake compared with non-targeted liposomes. The results suggested that L-FA-BAI could enhance anti-tumor efficiency and should be an effective FR-targeted carrier system for BAI delivery.

CAS / MDL: 21967-41-9 59-30-3
研究领域: 药剂学 · 肿瘤学 · 药物递送系统 · 纳米技术
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Polymer Chemistry · 2017 ·Vol. 8 ·期 20 ·3056-3065 · IF 5.375

“Click” functionalization of dual stimuli-responsive polymer nanocapsules for drug delivery systems

Wen Jing Yang,Tingting Zhao,Peng Zhou,Simou Chen,Yu Gao,Lijun Liang,Xiaodong Wang,Lianhui Wang

Surface decoration of nano-carriers is of great importance in targeted drug delivery systems. However, the surface coupling of functional ligands to nano-carriers usually involves sophisticated conjugation chemistry, such as carbodiimide-mediated amide coupling. Herein, “clickable” nanocapsules, containing reactive alkyne groups, were developed for surface functionalization via highly efficient thiol–yne click chemistry and further applied as intelligent drug nano-carriers. Firstly, by employing the facile reflux-precipitation polymerization, the “clickable” nanocapsules with dual thermal and redox responsive properties were readily prepared for further surface functionalization. The “clickable” nanocapsules were subsequently decorated with various functional ligands, including cysteine-folic acid, cysteine-RGD peptide and thiol-functionalized fluorescein isothiocyanate (SH-FITC). Finally, the folate acid-modified nanocapsules (FA-Nanocapsules) were explored as effective drug nano-carriers for doxorubicin (DOX) with triggered release behaviours due to the disulfide linkages and thermo-responsive poly(NIPAAm) components in the nanocapsules. The good growth inhibition of HeLa cells by DOX loaded FA-Nanocapsules indicated that the nanocapsules can be employed as promising drug delivery nano-carriers. The as-prepared dual stimuli-responsive nanocapsules, containing reactive alkyne groups, thus provide a versatile “clickable” platform for surface decoration and functionalization via highly efficient click chemistry.

CAS / MDL: 25316-40-9
研究领域: 药学 · 纳米技术 · 材料科学 · 生物医学工程
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Journal of Functional Foods · 2017 · IF 3.144

Fabrication of zinc (II) functionalized l-phenylalanine in situ grafted starch and its antibacterial activity and cytotoxicity

Chongyang Jin,Hualin Wang,Minmin Chen,Suwei Jiang,Qiusheng Song,Min Pang,Shaotong Jiang

A facile strategy was developed to fabricate zinc (II) functionalized l -phenylalanine in situ grafted starch (Zn(II)@ l -Phe-g-St). The structure of Zn(II)@ l -Phe-g-St was proposed and well characterized, and the assays of antibacterial activity against typical bacteria ( Bacillus subtilis and Escherichia coli ) and cytotoxicity of Hela cell were focused on. Boc- l -phenylalanine was used to achieve l -Phe-g-St by in situ grafting onto starch through esterification reaction after removal of Boc. It was confirmed that around 71.02% of NH 2 of l -Phe complexed with Zn(II) by σ-coordinate bonds and the coordination number of Zn(II) approximated to 2. Zn(II)@ l -Phe-g-St exhibited a good antibacterial activity against both Bacillus subtilis and Escherichia coli with increasing its concentration, and a relatively more effective antibacterial activity against Bacillus subtilis than Escherichia coli . Furthermore, Zn(II)@ l -Phe-g-St was found to be very low toxicity towards Hela cells especially at the concentration below 40   μg   ml −1 .

研究领域: 材料科学 · 生物技术 · 微生物学 · 毒理学
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Microsystems & Nanoengineering · 2024 ·Vol. 10 ·期 1 ·1-12 · IF 7.3

Bifunctional nanoprobe for simultaneous detection of intracellular reactive oxygen species and temperature in single cells

Ma Yanmei,Hu Weikang,Hu Jian,Ruan Muyang,Hu Jie,Yang Ming,Zhang Yi,Xie Hanhan,Hu Chengzhi

Living cells can rapidly adjust their metabolic activities in response to external stimuli, leading to fluctuations in intracellular temperature and reactive oxygen species (ROS) levels. Monitoring these parameters is essential for understanding cellular metabolism, particularly during dynamic biological processes. In this study, we present a bifunctional nanoprobe capable of simultaneous measurement of ROS levels and temperature within single cells. The nanoprobe features two individually addressable nanoelectrodes, with platinum (Pt) and nickel (Ni) coatings on both sides. At the tip, these two metal layers form a nano-thermocouple, enabling precise intracellular temperature measurements, while the Pt layer facilitates selective ROS detection. This dual functionality allows for real-time monitoring of cellular responses during synergistic chemo-photothermal therapy of cancer cells and zebrafish embryos subjected to mitochondrial toxic stress. Our results demonstrate that the nanoprobe effectively measures increases in temperature and ROS levels in HeLa cells undergoing chemo-photothermal therapy, as well as in chemically stimulated zebrafish embryos. By providing detailed analysis of submicrometer-scale temperature and ROS variations within living cells, this nanoprobe offers valuable insights into cellular processes and holds promise for early disease detection and drug development.

CAS / MDL: 7722-84-1
研究领域: 生物物理学 · 细胞生物学 · 纳米技术 · 癌症研究 · 发育生物学
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ACS Applied Materials & Interfaces · 2021 · IF 9.229

Intracellular Paclitaxel Delivery Facilitated by a Dual-Functional CPP with a Hydrophobic Hairpin Tail

Yuping Wei,Man Zhang,Pengfei Jiao,Xin Zhang,Ganggang Yang,Xia Xu

In our pervious study, a dual-functional peptide R7 was developed to form a complex with paclitaxel (PTX) for enhancement of PTX translocation. However, because of the unstable noncovalent bond between R7 and PTX, PTX redistributed after the introduction of heparin, leading to R7-PTX complex dissociation, further causing less PTX penetration than expected. Thus, a novel positive CPP carrier of P9 was developed to improve CPP-PTX affinity via a double-proline (Pro, P) hairpin tail and enhance PTX translocation through the reduction of translocation energy barrier, confirmed by the MM-PBSA analysis and umbrella sampling simulation. Cellular uptake study reveals that P9 can quickly translocate into the HeLa cells within 1 min and exhibits no noticeable cytotoxicity. Compared to R7, P9 is able to help PTX translocation, leading to a remarkable increase in the intracellular concentration of PTX, eventually resulting in a significant loss in tumor cell viability. In vivo experiments demonstrate that a vein injection of P9-PTX complex dramatically inhibits tumor growth. Our study provides a novel perspective for designing CPP-facilitated drug carrier to enhance antitumor efficiency.

研究领域: 药学 · 生物技术 · 癌症研究 · 分子生物学
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COLLOIDS AND SURFACES B-BIOINTERFACES · 2018 · IF 3.997

A dual-sensitive mesoporous silica nanoparticle based drug carrier for cancer synergetic therapy

Jing Zhang,Biao Shen,Liqun Chen,Lingdong Chen,Yangsheng Meng,Jie Feng

A multifunctional envelope-type mesoporous silica nanoparticle (MSN) was delicately designed for subcellular co-delivery of drug and therapeutic peptide to tumor cells. Firstly, a kind of cell apoptosis peptide (KLAKLAK) 2 (KLA) was anchored on surface of MSN via disulfide bond to obtain MSN-SS-KLA. Subsequently, anticancer drug doxorubicin hydrochloride (DOX) was loaded into the pores of MSN-SS-KLA. Then, the drug loaded MSN-SS-KLA (DOX@MSN-SS-KLA) was further coated with bovine serum albumin (BSA) to obtain a biological media stable MSN based drug delivery system (DDS), DOX@MSN-SS-KLA/BSA, for cancer synergetic therapy. The results show that stability of the DOX@MSN-SS-KLA/BSA is much better than that of DOX@MSN-SS-KLA and it could keep well dispersed in serum for more than 24 h. After accumulating at tumor site by EPR effect, the DOX@MSN-SS-KLA/BSA could be effectively phagocytosed by HeLa cells and release apoptotic peptide KLA as well as DOX simultaneously responding to reductive stimulus inside the cells. In vitro cell experiment results show that the DOX@MSN-SS-KLA/BSA complex exhibits much better inhibition on HeLa cells compared with pure DOX, indicating that co-delivery of KLA and DOX is expected to achieve synergetic therapy of cancer.

研究领域: 纳米技术 · 药学 · 癌症研究 · 生物医学工程
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