ACS Applied Materials & Interfaces
·
2016
·
IF 7.145
Yi Zhang,Junkun Duan,Lingguang Cai,Dong Ma,Wei Xue
For cancer gene therapy, a safe and high-efficient gene carrier is a must. To resolve the contradiction between gene transfection efficiency and cytotoxicity, many polymers with complex topological structures have been synthesized, although their synthesis processes and structure control are difficult as well as the high molecular weight also bring high cytotoxicity. We proposed an alternative strategy that uses supramolecular inclusion to construct the aggregate from the small molecules for gene delivery, and to further explore the relationship between the topological assembly structure and their ability to deliver gene. Herein, PEI-1.8k-conjugating β-CD through 6-hydroxyl (PEI-6-CD) and 2-hydroxyl (PEI-2-CD) have been synthesized respectively and then assembled with diferrocene (Fc)-ended polyethylene glycol (PEG-Fc). The obtained aggregates were then used to deliver MMP-9 shRNA plasmid for MCF-7 cancer therapy. It was found that the higher gene transfection efficiency can be obtained by selecting PEI-2-CD as the host and tuning the host/guest molar ratios. With the rational modulation of supramolecular architectures, the aggregate played the functions similar to macromolecules which exhibit higher transfection efficiency than PEI-25k, but show much lower cytotoxicity because of the nature of small/low molecules. In vitro and in vivo assays confirmed that the aggregate could deliver MMP-9 shRNA plasmid effectively into MCF-7 cells and then downregulate MMP-9 expression, which induced the significant MCF-7 cell apoptosis, as well inhibit MCF-7 tumor growth with low toxicity. The supramolecular aggregates maybe become a promising carrier for cancer gene therapy and also provided an alternative strategy for designing new gene carriers.
研究领域:
生物化学
·
分子生物学
·
药学
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产品关联
DOI
PubMed
高影响因子
Toxics
·
2026
·Vol. 14
·期 3
·222
·
IF 4.9
Xiao Kang,Wenting Song,Xueyan Li,Yuyan Yang,Xinke Wu
Breast cancer is the most common malignant tumor among women worldwide, and its occurrence is closely associated with long-term exposure to environmental pollutants. Polycyclic aromatic hydrocarbons (PAHs) are a class of persistent organic pollutants widely present in the living environment. Epidemiological studies indicate that exposure to PAHs increases the risk of breast cancer. PAH derivatives exhibit stronger toxicity or endocrine-disrupting activity than their parent compounds; however, research on their specific effects and mechanisms in breast cancer cells remains limited. For this purpose, this study selected 3-Hydroxybenz[a]anthracene, a PAH derivative with potential estrogenic activity, as the target compound. Using the estrogen receptor-positive breast cancer cell line MCF-7 as the model, we performed EdU staining, colony formation assays, scratch healing assays, Transwell invasion assays, and apoptosis assays and preliminarily examined changes in relevant signaling proteins via Western blot. Results indicate that 3-Hydroxybenz[a]anthracene promotes proliferation and migration in MCF-7 cells while inhibiting apoptosis under certain conditions, but it has no effect on cell invasion. Mechanistically, it upregulates key proteins including AKT, c-Myc, E-Cadherin, Vimentin, MMP2, MMP9 and Bcl-2 while downregulating p-AKT expression. This study confirms through in vitro experiments that 3-Hydroxybenz[a]anthracene exhibits estrogen-like effects and modulates malignant behavior in breast cancer cells by regulating relevant signaling pathways. These findings provide experimental evidence for further evaluating the potential role of this environmental contaminant in breast cancer initiation and progression.
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DOI
PubMed
高影响因子
RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY
·
2025
·Vol. 51
·期 6
·2582-2592
·
IF 1.7
Wang Yong,Liu Li-Na,Wei Shang-Hua,Wang Wei,Liu Cong-Jun,Gao Song,Yu Shu-Ping,Yao Ning,Wang Yu-Fei
Objective: Dehydroabietic acid (DHAA) is an important natural triterpene resin acid with a wide range of pharmacological activities, including antibacterial, antifungal, antiviral, and anti-inflammatory effects, particularly in antitumor activity. The aim of this study was to synthesize a series of novel dehydroabietic acid 1,2,3-triazole derivatives and evaluate their antitumor activity. Methods: Click chemistry was employed to conjugate dehydroabietic acid (DHAA) with 1,2,3-triazole, yielding 12 DHAA derivatives containing 1,2,3-triazole with yields ranging from 64.5 to 90%. The structures of the target compounds were confirmed by 1 H, 13 C NMR, and HR-MS (ESI). The initial antiproliferative activity of these compounds was assessed in vitro using two tumor cell lines (human cervical cancer cells, HeLa, and human breast carcinoma cells, MCF-7), with cisplatin used as a reference. Results and Discussion: The results indicated that three compounds, VII , VIII , and IX , exhibited significant antiproliferative activity against the tumor cell lines. Among them, compound VIII (4-(4-fluorophenyl)-1-(((1 R ,4a S )-7-isopropyl-1,4a-dimethyl-1,2,3,4,4a,9,10,10a-octahydrophenanthren-1-yl)methyl)-1 H -1,2,3-triazole) demonstrated particularly remarkable activity, with an IC 50 value of 22.1 μM against HeLa cells and 23.2 μM against MCF-7 cells. Conclusions: This study provides useful strategies for the design and synthesis of novel antitumor agents. The synthesized compounds exhibit some inhibitory effects on tumor cell growth and proliferation while causing minimal damage to normal cells, warranting further investigation.
研究领域:
药物化学
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肿瘤学
·
有机合成
·
药理学
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天然产物研究
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产品关联
DOI
高影响因子
Frontiers in Pharmacology
·
2020
·
IF 4.225
Yan Huijie,You Yun,Li Xinjian,Liu Lei,Guo Fengqian,Zhang Qiongling,Liu Dewen,Tong Yan,Ding Shilan,Wang Jinyu
Pharmacological Relevance: Paclitaxel (PTX) is currently the only botanical drug that can control the growth of cancer cells. Paclitaxel is widely used in the treatment of breast cancer, ovarian cancer, uterine cancer, non-small cell lung cancer and other cancers.Aim: Folate receptor and integrin αvβ3 are highly expressed on the surface of human breast cancer cells MCF-7. Folic acid and arginine-glycine-aspartate (Arg-Gly-Asp, RGD) tripeptide sequence have a high affinity for folate receptor and integrin αvβ3, respectively. To enhance the effect on breast cancer, we constructed the folate acid and RGD peptide dual-targeted (MSNs-NH2-FA-RGD) drug-carrier based on mesoporous silica nanoparticles.Methods: The structure of mesoporous nanocarriers was characterized by Fourier transform infrared spectroscopy, nitrogen adsorption-desorption analysis, transmission electron microscopy, laser particle size analyzer, and thermogravimetric analysis. Paclitaxel was chosen as the model drug. The targeting-ability was verified by observing the uptake of mesoporous carriers loaded with rhodamine in MCF-7, MCF-10A, and HeLa cells using a fluorescence microscope. The cytotoxicity of the blank carrier MSNs-NH2-FA-RGD and the efficacy of the drug carrier PTX@MSNs-NH2-FA-RGD were assessed by cell experiments.Results: The characterization showed successful construction of a dual-targeted mesoporous silica nanocarrier. Obvious differences were detected in the fluorescence intensity of the three cell lines. The results of the pharmacological tests indicated that the blank nanoparticles do not cause any apparent toxicity on these cells. The IC50 of free PTX and PTX@MSNs-NH2-FA-RGD on MCF-7 cells line treated for 48 h were 35.25±2.57 ng·ml-1 and 22.21±3.4 ng·ml-1 respectively, which indicated that the inhibitory efficacy of PTX@MSNs-NH2-FA-RGD on MCF-7 was 1.6 times than that of free PTX.Conclusions: The dual-targeted nanocarrier MSNs-NH2-FA-RGD could target breast cancer cells, and sever as a potential candidate in future of drug development.
研究领域:
药理学
·
纳米医学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR LIQUIDS
·
2022
·
IF 6.633
Danfeng Wang,Min Liu,Yushu Wu,Tianxin Weng,Lu Wang,Yongfang Zhang,Yanna Zhao,Jun Han
The co-loading of chemotherapy-phototherapy (CTPT) combination drugs by aptamer-targeted DNA nanostructures has significant advantages in improving anticancer effects and overcoming the multidrug resistance of cancer cells. The different binding modes of drugs to DNA nanostructures may impact CTPT therapy. Here, the anti-drug resistance effects of idarubicin (IDA) or acridine orange (AO) as single drug, as well as IDA/mithramycin (MTR) dimers ((MTR) 2 Zn 2+ ) + AO combination drugs loaded by AS1411-tethered DNA nanotrains (AS1411NTrs), were studied. The intercalative binding mode between IDA/AO and AS1411NTrs was verified through measurements of viscosity, changes in melting temperature, and potassium iodide quenching. A series of thermodynamic parameters such as the binding constant and the number of binding sites were obtained through fluorescence spectroscopy, isothermal titration calorimetry, and differential scanning calorimetry. The high binding constants and the number of binding sites indicated that AS1411NTrs had a high loading capacity for IDA and AO. An in vitro release study showed that the release rate and release model of IDA/(MTR) 2 Zn 2+ /AO in the binary and ternary systems with or without deoxyribonuclease I were related to their binding mode and order of addition. An in vitro cytotoxicity study proved that the cytotoxicity and synergistic effects of the three drugs to human breast cancer MCF-7 cells and multidrug-resistant MCF-7/ADR cells were enhanced due to loading of AS1411NTrs. The IDA/(MTR) 2 Zn 2+ + AO combination drugs could more obviously enhance apoptosis of MCF-7/ADR cells as confirmed by cell apoptosis assays. The cell uptake study demonstrated that IDA/(MTR) 2 Zn 2+ /AO loaded by AS1411NTrs was mainly concentrated in the nucleus of MCF-7/ADR cells. This work will provide theoretical information for combination therapy of IDA/(MTR) 2 Zn 2+ and AO based on DNA nanostructures.
研究领域:
药学
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纳米技术
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癌症研究
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生物物理学
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分子生物学
✓ 已验证
产品关联
DOI
高影响因子
Science of Advanced Materials
·
2021
·Vol. 13
·期 7
·1295-1303
·
IF 1.474
Liu Guangheng,Yang Xiangfeng,Niu Qiming,Sun Wenkui
ABSTRACT
A new type of difolate targeting nano-level ultrasound contrast agent ((folate molecule, FOL)2-TUAs) was prepared, so as to investigate its targeted binding effect with human breast cancer mammary carcinoma cells (MCF-7) in vitro. L-2-aminoadipic
acid (L-2-AD) as a branch unit was inserted at the hydroxyl end of distearoyl phosphatidylethanolamine (DISP)-PEG2000-COOH to construct a tree structure. At this time, the free hydroxyl group in the distearoyl phosphatidylethanolamine (DISP)-PEG2000-COOH structure modified the FOL with the
help of N-Hydroxysuccinimide/N,N'-dicyclohexylcarbodiimide (NHS/DCC). Each 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DISP-PEG2000) connected two FOLs to generate difolate targeted nanomaterials. Nano laser particle size (PS)
and Zeta potential analyzer (ZPA) were applied to analyze the physical characteristics of the material such as PS and dispersion, and the enhanced development effect in vitro was detected by the ultrasonic diagnostic instrument. Besides, the targeted binding ability of the contrast
agent based on this material to folate receptor (FR) overexpressing MCF-7 cells was analyzed by flow cytometry (FCM) and fluorescence microscope. In the experiment, hydrogen-1 nuclear magnetic resonance (1H NMR) demonstrated that (FOL)2-TUAs was successfully synthesized.
The surface of this material was round and uniformly distributed without aggregation. According to the relative number of FOL molecules, non-targeted nano-agent (U-TUA), monofolate targeted nano-agent (FOL-TUA), and difolate targeted nano-agent ((FOL)2-TUA) were obtained. The in
vitro imaging showed that different materials exhibited enhanced imaging effects in ultrasonic diagnostic equipment. FCM and fluorescence microscopy both indicated that the difolate TUA could achieve a good binding to MCF-7 cells. Most of the nano-agents were attached to the cell membrane,
surrounded by red fluorophore, namely increasing the FOL content of DISP-PEG2000 chain could enhance the targeted binding ability of tumor cells.
研究领域:
肿瘤学
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医学影像学
·
药剂学
✓ 已验证
DOI
高影响因子
Phytochemistry Letters
·
2025
·
IF 1.4
Yan-Mei Wu,Jing-Ya Mo,Yong-Yan Mei,Quan Liu,Yuan-Yuan Huang,Bei Zhou,Yi-Hang Li,Yan-Chun Wu,Jing-Quan Yuan
Trichodones D-F ( 1 - 3 ), three previously undescribed polyketide compounds featuring conjugated α - β -unsaturated ketone moieties, were isolated from the endophytic fungus Trichoderma protrudens associated with the semi-mangrove plant Hibiscus tiliaceus Linn. The structural elucidation of these compounds was accomplished through the analysis of 1D and 2D NMR spectra, complemented by HR-ESI-MS data. The absolute configurations were determined through comparative analysis of experimental CD and calculated ECD spectra. Additionally, the cytotoxic activities of compounds 1 - 3 against the human breast cancer cell line MCF-7 and the human hepatocellular carcinoma cell line HepG2 were evaluated using the CCK8 assay. Notably, compound 3 exhibited moderate inhibitory activity against HepG2 and MCF-7 cell lines with IC 50 values of 22.7 μM and 55.1 μM, respectively.
研究领域:
药理学
·
有机化学
·
肿瘤学
✓ 已验证
DOI
高影响因子
Small Methods
·
2020
·Vol. 5
·期 4
·2001047
·
IF 12.13
Jianqiao Chang,Yu Zhang,Yike Li,Ziwei Han,Fei Tian,Chao Liu,Qiang Feng,Yuguang Wang,Jiashu Sun,Lu Zhang
Detection of mRNA expression in live cells during treatment is a challenging task, despite its importance in tumor biology and potential therapeutic leads. Here a multilayer ratiometric fluorescent nanomachine for live-cell perturbation and imaging of mRNA at single cell resolution is reported. The nanomachines fabricated by microfluidic approaches consist of fluorescent polymeric cores and multiple lipid layers, which can efficiently deliver siRNA and molecular beacons (MBs) to cytosol and then release the cargo in a sequential way. The siRNA molecules released from the outer lipid layers lead to silencing of multidrug resistance 1 (MDR1) gene, and the MBs from the middle lipid layers detect the presence of MDR1 mRNA. The fluorescent ratio of MBs to fluorescent polymeric cores positively correlates with the expression level of MDR1 mRNA in MCF-7/ADR cells during siRNA treatment. The nanomachines provide comparable results with traditional qPCR for quantifying mRNA, showing great potential for modulation and imaging of intratumoral mRNA in vitro and in vivo.
研究领域:
生物技术
·
分子生物学
·
癌症研究
·
纳米技术
✓ 已验证
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2023
·
IF 9.5
Xiaoming Su,Yangcenzi Xie,Xinyu Liu,Mingyang Chen,Chao Zheng,Hong Zhong,Ming Li
Exosomes (exos) widely existing in body fluids show great potential for noninvasive cancer diagnosis. Quantitative analysis of exos is traditionally performed by targeting specific exosomal surface proteins, but it is often imprecise due to the common expression of exosomal proteins and subtle expression differences between different cancer subtypes. Herein, we report quantitative surface-enhanced Raman spectroscopy (SERS) of serum exos through a combination of a paper-based lateral flow strip (LFS) biosensor with multivariate spectral unmixing analysis rather than simply quantifying exosomal proteins. Our SERS-LFS biosensor enables absolute quantification of two different serum exos with a limit of detection down to ∼106 particles/mL for both exos. We further exemplify the application of this strategy in quantitative dual-plex detection of serum exos from breast cancer patients. We find that human epidermal growth factor receptor 2+ (HER2+) and luminal A breast cancer patients undergoing no surgery are enriched in serum exos derived from SKBR-3 cells and MCF-7 cells (denoted as SKBR and MCF exos), respectively. The surgical treatment of these breast cancer patients accompanies an obvious decrease of either SKBR or MCF exos in the serum. These results suggest the great potential of the combination of the SERS-LFS biosensor and multivariate spectral unmixing for breast cancer subtyping and therapeutic surveillance with the powerful quantitative capability of exos in clinical samples.
研究领域:
生物医学工程
·
癌症诊断
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2021
·
IF 5.34
Lei Yu,Shuang Han,Lang Lang,Hui Song,CaiYun Zhang,Lin Dong,ShaoHua Jia,Ying Zhang,Di Xiao,Jun Liu,Ying Xu,XiaoPo Zhang
Background DNA topoisomerase (Topo) inhibition plays key role in breast cancer treatment. Stephania hainanensis H. S. Lo et Y. Tsoong ( S. hainanensis ), a Li nationality plant that has abundant aporphine alkaloids , can inhibit Topo. Purpose To identify a dual Topo inhibitor , a deep and systematic study of active aporphine alkaloids in S. hainanensis and their mechanisms of inhibiting breast cancer proliferation and Topo activity are essential. Study design This study aimed to assess the anti-breast cancer and Topo inhibitory activities of oxocrebanine and explore the underlying mechanisms. Methods The growth inhibitory activities of 12 compounds in S. hainanensis were screened by MTT assay in MCF-7, SGC-7901, HepG-2 cells, and compared with the effects on human normal mammary epithelial MCF-10A cells as non cancer control cells. The Topo inhibitory activity was assessed by DNA relaxation and unwinding assays, kDNA decatenation assay and western blot . Cell cycle and autophagy analyses were carried out with flow cytometry and staining. Acridine orange staining and α-tubulin morphology were observed by fluorescence microscopy . Western blot was used to examine microtubule assembly dynamics and the expression levels of key proteins associated with DNA damage, autophagy and mitotic arrest . Results Oxocrebanine was the anti-breast cancer active alkaloid in S. hainanensis . It exhibited the best inhibitory effect on MCF-7 cells with an IC 50 of 16.66 μmol/l, and had only weak effect on the proliferation of MCF-10A cells. Oxocrebanine inhibited Topo I and II α in a cell-free system and in MCF-7 cells. The DNA unwinding assay suggested that oxocrebanine intercalated with DNA as a catalytic inhibitor. Oxocrebanine regulated the levels of Topo I and IIα and DNA damage-related proteins. Oxocrebanine led to the mitotic arrest, and these effects occurred through both p53-dependent and p53-independent pathways. Oxocrebanine induced autophagy, abnormal α-tubulin morphology and stimulated enhanced microtubule dynamics. Conclusion Oxocrebanine was the anti-breast cancer active aporphine alkaloid in S. hainanensis . Oxocrebanine was a Topo I/IIα dual inhibitor, catalytic inhibitor and DNA intercalator . Oxocrebanine caused DNA damage, autophagy, and mitotic arrest in MCF-7 cells. Oxocrebanine also disrupted tubulin polymerization. Accordingly, oxocrebanine held a great potential for development as a novel dual Topo inhibitor for effective breast cancer treatment.
研究领域:
癌症研究
·
药理学
·
分子生物学
·
植物化学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
Nanoscale
·
2013
·Vol. 5
·期 5
·2107-2113
·
IF 6.233
Leyong Zeng,Wenzhi Ren,Lingchao Xiang,Jianjun Zheng,Bin Chen,Aiguo Wu
Multifunctional Fe3O4–TiO2 nanocomposites with Janus structure for magnetic resonance imaging (MRI) and potential photodynamic therapy (PDT) were synthesized, in which Fe3O4 was used as a MRI contrast agent and TiO2 as an inorganic photosensitizer for PDT. Their morphology, structure, and MRI and PDT performance were characterized, respectively. Moreover, the location of Fe3O4–TiO2 nanocomposites in MCF-7 cells was also investigated by the staining of Prussian blue and alizarin red, respectively. The results showed that the as-prepared Fe3O4–TiO2 nanocomposites had good T2-weighted MRI performance, and the MCF-7 cells incubated with nanocomposites could be killed under the irradiation of UV light. Compared with traditional organic photosensitizers, TiO2 inorganic photosensitizers could have more stable PDT performance due to their nanoscale size and anti-photodegradable stability. Therefore, the as-prepared Fe3O4–TiO2 nanocomposites could have potential applications as a new kind of multifunctional agent for both MRI and PDT.
研究领域:
生物医学工程
·
材料科学
·
医学影像
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Sensors
·
2018
·
IF 5.711
Qian Han,Jianping Liu,Qingtao Meng,Yong-Lei Wang,Huan Feng,Zhiqiang Zhang,Zhi Ping Xu,Run Zhang
An effective bioanalytical method for rapid, sensitive, specific, and in situ sensing of nitric oxide (NO) is the key for further unveiling the biological functions of this gasotransmitter molecule in vitro and in vivo. In this contribution, a new fluorescence probe for sensing and imaging of NO in live systems was developed. The probe, FP-NO, was designed by exploring a novel sensing mechanism, i.e., the rotation of the N–N single bond of a coumarin derivative. FP-NO was prepared by incorporating a recognition unit, thiosemicarbazide moiety into a coumarin fluorophore. The weakly fluorescent FP-NO quickly and selectively reacts with NO to form a highly fluorescent product, FP-P. Such an enhancement of fluorescence emission allows NO detection with high sensitivity. The detection limit was 47.6 nM. The reaction mechanism was validated by HRMS titration analysis and the “OFF-ON” fluorescence response mechanism was rationalized by theoretical computation. FP-NO is biocompatible and live cell membrane permeable. The feasibility of FP-NO as the fluorescence probe for imaging and flow cytometry analysis of exogenous NO in MCF-7 cells and exogenous NO production in inflamed J774A.1 macrophage cells was then evaluated. Visualization of exogenous and endogenous NO production in live zebrafish was then achieved, implying the potential application of FP-NO in the studies of the NO roles in live organisms.
研究领域:
生物化学
·
分子生物学
·
医学影像学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）