International Journal of Nanomedicine
·
2025
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IF 6.5
ZhiFeng Chen,WenLing Liu,ZiJian Zeng,ZhiHong Yan,LiHeng Ma,Yi Liu,XianShuo Cao
Purpose This study designed a dopamine derivative integrating active targeting and pH-responsive borate ester bond-mediated passive targeting to construct drug delivery systems for tumor-targeted drug delivery, thus improving antitumor drug bioavailability and expanding the application of dopamine in drug delivery.Methods Nuclear magnetic resonance and Fourier transform infrared spectrometry were used to determine the structures of Man-PBA-DAO and Man-2PBA-DAO. Hydrodynamic diameter measurements confirmed the pH responsiveness of the targeting nanoparticles in different pH media over 12 hours. Nanoparticle toxicity was assessed using the MTT assay. Cellular uptake of the targeting nanoparticles was evaluated using flow cytometry and fluorescence microscopy. High-performance liquid chromatography (HPLC) was employed to quantify curcumin content.Results Covalent binding of mannose molecules to the dopamine derivative molecule allowed it to specifically target A549 cells with mannose receptors. More importantly, a significantly accelerated drug release (about 62% at pH=5.0) at low pH values was achieved by regulating the number of acidic-responsive borate bonds in polymer main chains. As a result, due to active targeting of mannose and passive targeting of acid response, Curcumin-loaded nanoparticles offer remarkably enhanced inhibiting efficiency against A549 cells at a low concentration of 6.25 μg/mL.Conclusion The dopamine derivative Man-2PBA-DAO-constructed dual active-passive targeting nano micelles enabled precise delivery and controllable release of Cur, offering new prospects for dopamine-based drug delivery in lung cancer treatment.
研究领域:
药剂学
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纳米技术
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肿瘤学
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材料科学
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生物化学
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产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2016
·
IF 4.219
Fangfang Xu,Kangsheng Liao,Yunshan Wu,Qi Pan,Lilan Wu,Hong Jiao,Dean Guo,Ben Li,Bo Liu
Extraction optimization, purification, characterization, sulfation and antitumor activity of polysaccharides from the fruit body of Borojoa sorbilis cuter were investigated in present study. The optimal Ultrahigh Pressure extraction condition was determined as: extraction once with the solid-liquid ratio of 1:10 in 30 °C and 1500 Mpa for crude polysaccharide (BP) and experimental yield was 8.28%. Four water-soluble polysaccharides named as BP1-1, BP1-2, BP1-3 and BP1-4, with molecular weight of 35.8, 32.4, 30.1 and 27.7 kDa, were purified by DEAE Sepharose and Superdex 200 chromatography. On the basis of chemical and spectroscopic analyses, BP1-1–BP1-4 were found to be neutral β- d -galactan containing a (1 → 4)-linked backbone. S-BP1s with the DSS of 1.18, was sulfated by chloro-sulfonic acid-pyridine method. Furthermore, S-BP1s exhibited significant in vitro antitumor activity against liver cancer HepG2 and lung cancer A549 cells in a dose-dependent manner. The results indicated that S-BP1s could be potentially developed as functional antitumor drug.
研究领域:
药理学
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生物化学
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分子生物学
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癌症研究
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DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2023
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IF 8
Cancheng Liao,Danqiao Xu,Xiaohong Liu,Yuqi Fang,Jun Yi,Xiaofang Li,Bohong Guo
Background and aim Iridium (Ir)-based complex is a potential antitumor ingredient, but its poor physicochemical properties such as hydrophobicity and low biocompatibility hamper further application. Liposome provides a potential delivery approach for improving the poor physicochemical property and reducing the side effects of antitumor drug. In this study, we aimed at incorporating Ir ([Ir(ppy)2(BTCP)]PF6) into liposomes to enhance the biocompatibility and sustained release of Ir for intravenous administration and to elucidate the mechanism in A549 cells.Materials and methods Ir-loaded PEGylated liposomes (Lipo-Ir) were formulated by thin-film dispersion and ultrasonic method. Morphology, size distribution, and zeta potential of Lipo-Ir were examined by transmission electron microscopy (TEM) and Zetasizer. The released profile and biocompatibility were investigated by dialysis method and hemolysis test, respectively. Additionally, the cytotoxic activity and mechanism of Lipo-Ir and Ir inducing apoptosis in A549 cells were evaluated.Results Lipo-Ir can keep sustained release, excellent biocompatibility, and physical stability. The average particle size, polydispersity index, zeta potential, encapsulation efficiency, and drug loading are 112.57±1.15 nm, 0.19±0.02, −10.66±0.61 mV, 94.71%±3.21%, and 4.71%±0.41%, respectively. 3-(4,5-dimethylthiazole)-2,5-diphenltetraazolium bromide (MTT) assay show that Lipo-Ir and Ir display high cytotoxicity against selected cancer cells. Furthermore, the apoptotic features of morphology, depolarization of mitochondrial membrane potential, increase in the reactive oxygen species (ROS) levels, and disorder of Ca2+ homeostasis are observed after treating A549 cells with Ir and Lipo-Ir. Besides, Lipo-Ir can arrest the cell growth in G0/G1 phase.Conclusion The studies demonstrate that Lipo-Ir can trigger apoptosis in A549 cells via ROS-mediated mitochondrial dysfunctions, and the biocompatible and sustained Lipo-Ir will be a promising drug delivery system.
研究领域:
药理学
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肿瘤学
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分子生物学
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化疗
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产品关联
DOI
PubMed
高影响因子
CELLULAR SIGNALLING
·
2023
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IF 4.8
Yingying Chen,Zhong He,Bo Zhao,Rui Zheng
Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease and a severe form of pulmonary fibrosis. Epithelial-mesenchymal transition (EMT) of alveolar epithelial cells is induced in response to epithelial injury, which leads to the accumulation of extracellular matrix in the lung parenchyma and contributes to pulmonary fibrosis. NPAS2 (neuronal PAS domain protein 2) is significantly increased in the lung tissues of IPF patients according to microarray dataset GSE10667 and NPAS2 is downregulated in differentiated human pulmonary type 2 epithelial cells in vitro based on microarray dataset GSE3306 from Gene Expression Omnibus (GEO). In this study, we demonstrated that NPAS2 was increased in bleomycin (BLM)- induced fibrotic lungs in mice. Knockdown of NPAS2 inhibited EMT in primary mouse lung alveolar type 2 epithelial (pmATII) cells and human lung alveolar type 2 epithelial cell line A549 cells under BLM challenge in vitro. Moreover, the silence of NPAS2 alleviated the BLM-induced pulmonary fibrosis in a murine model. Mechanistically, NPAS2 promotes EMT through positively regulating hairy and enhancer of split 1 (HES1) expression. In this study, we present novel findings that have not been previously reported, emphasizing that p53 transcriptionally activates NPAS2 in ATII cells and overexpression of NPAS2 weakens the effects of TP53 knockdown on EMT of pmATII and A549 cells. Our results suggest NPAS2 is a novel target gene of p53 in regulating BLM-mediated EMT in ATII cells and pulmonary fibrosis.
研究领域:
呼吸病学
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分子生物学
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细胞生物学
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基因组学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL RESEARCH IN TOXICOLOGY
·
2026
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IF 4.1
Zihan Li,Boxuan Xie,Xilei Liu,Zihan He,Zhongwei Zhang,Jianming Zhou,Tong Zhou,Huai Wang
As the most frequently occurring cancer worldwide, lung cancer is notoriously diagnosed at advanced stages, resulting in high mortality rates. The primary factor underlying this persistent global health burden remains tobacco consumption. Nicotine, a key component of cigarette smoke, is one of the major contributing factors to the development of lung cancer, but the molecular mechanisms remain incompletely elucidated. α7-nAChR, β2-AR, and HGF/c-Met are known to contribute to lung cancer development, respectively. However, the specific signaling cascade through which they interact in nicotine-induced malignancy is unclear. In this study, using CCK-8 assays across a range of concentrations (0–5 μM), we determined that 1 μM nicotine treatment for 48 h optimally enhances A549 cell proliferation, establishing this condition for subsequent experiments. This study uncovers nicotine’s role in driving malignant behaviors including proliferation, migration, and invasion in nonsmall cell lung cancer A549 cells. Notably, nicotine potently stimulated migration and invasion, accompanied by upregulation of Cyclin D1 and MMP-2, and downregulation of BAX, BAD, and Caspase-3. Mechanistically, nicotine induced synergistic engagement of α7-nAChR and β2-AR, leading to activation of the HGF/c-Met/PI3K/AKT axis and enhancing the secretion of both HGF and MMP-2. Importantly, we reveal a previously unrecognized bidirectional regulatory loop between α7-nAChR and β2-AR that functionally converges on the HGF/c-Met axis, which acts as a critical signaling hub to drive the downstream PI3K/AKT pathway and facilitate tumor progression. Our findings provide the first evidence of a coordinated α7-nAChR/β2-AR interface regulating HGF/c-Met signaling that orchestrates both intracellular signaling and extracellular secretory programs in nicotine-promoted lung cancer progression. This offers innovative insights for identifying potential antitumor therapeutic targets and presents novel perspectives for the prevention and clinical management of lung cancer, particularly in smokers with nonsmall cell lung cancer.
✓ 已验证
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2018
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IF 3.997
Chaoyang Li,Hua Zhang,Xianfeng Gong,Qiang Li,Xueling Zhao
The chemical stability, good biocompatibility and high drug loading capacity of zinc oxide nanoparticles (ZnO NPs) and their biomedical potentials make them a promising candidate for drug delivery. The aim of this study was to develop and assess a simple procedure for surface functionalization of ZnO NPs by N-acetyl- l -cysteine (NAC) for anticancer camptothecin (CPT) delivery. NAC capped ZnO NPs were successfully made using ZnCl 2 and NaOH in the presence of NAC. CPT was covalently conjugated to the surface of as-synthesized ZnO-NAC NPs. To characterize the synthesized conjugate product (ZnO-NAC-CPT NPs), X-ray diffraction, Fourier Transform Infrared spectroscopy, transmission electron microscopy, scanning electron microscopy, and dynamic light scattering method were used. Our results indicated that the ZnO-NAC-CPT NPs exhibit near-spherical morphology and uniform dispersion with an average diameter of ∼70 nm. The hemolysis assay showed that ZnO-NAC-CPT NPs has almost no hemolytic activity. In addition, MTT cytotoxicity assessment on A549 lung cancer cells revealed a drop of IC 50 values from 1.17 μg/mL (free CPT) to 0.66 μg/mL (ZnO-NAC-CPT NPs). This result showed an augmented cancer-inhibitory effect of nanoconjugate complex. In conclusion, the novel ZnO-NAC-CPT NPs could be considered for new therapeutic endeavors.
研究领域:
纳米技术
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药学
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癌症研究
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2017
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IF 3.649
Yingqi Xu,Shengpeng Wang,Hon Fai Chan,Yuling Liu,Hui Li,Chengwei He,Zeyong Li,Meiwan Chen
Mitochondria are important targets for the intracellular delivery of drugs and DNA. For mitochondria-targeted delivery, a mitochondriotropic molecule, triphenylphosphonium (TPP), was applied to the synthesis of amphiphilic TPP-poly(ethylene glycol)-poly(ε-caprolactone) (TPP-PEG-PCL) polymers. The TPP-PEG-PCL polymer was used to prepare micelles using a solvent evaporation method for the delivery of gambogic acid (GA) (GA-TPP). The micelles were obtained with a favorable particle size of 150.07 ± 11.71 nm and an encapsulation efficiency of 80.78 ± 1.36%, and they displayed homogeneous spherical shapes. The GA-TPP micelles exerted enhanced cytotoxic and pro-apoptotic effect against A549 cells compared to free GA and GA-loaded PEG-PCL (GA-PP) micelles, due to the inhibition of the expression of apoptosis-related proteins and promotion of caspase 3/7 and caspase 9 activity. Notably, the mitochondria-targeting GA-TPP micelles selectively accumulated in the mitochondria, inducing the loss of mitochondrial membrane potential and the release of cytochrome c , thereby achieving improved mitochondria-targeting effects. In conclusion, the GA-TPP micelle system shows great promise for lung cancer treatment by inducing an apoptotic effect via the mitochondrial signaling pathway.
研究领域:
药物学
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材料科学
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肿瘤学
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
CURRENT PHARMACEUTICAL DESIGN
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2025
·Vol. 31
·期 42
·3416-3426
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IF 2.8
Chenguang Yao,Ting Tan,Jiangning Yan,Zijia Zhao,Romina Onintsoa Diarimalala,Junjie Wang,William Wang,Hanluo Li,Jingbiao Liu,Yanhong Wei,Kanghong Hu
ObjectiveTo develop new Anderson-type polyoxometalates (POMs) with high efficiency and low cytotoxicity, and investigate the effects and mechanisms against lung (A549), cervical (Hela), and breast cancer (MCF7) cell lines.MethodsCytotoxicity assessments on Hela, A549, and MCF-7 tumor cells were tested by MTT assay. Antitumor activities of B1 (vanadium-centered, methyl-modified) and B7 (vanadium-centered, hydroxyl-modified) were detected by apoptosis, scratch, and colony formation assay. The antitumor molecular mechanisms were explored by Western blotting.ResultsThis study synthesized and evaluated twelve Anderson-type compounds which were centered with vanadium, chromium, iron, cobalt, nickel, and copper heteroatoms, modified with methyl and hydroxyl at the side chains. Cytotoxicity assessments revealed that compounds B1 and B7 exhibited superior efficacy, with IC50 values of approximately 7 μmol/L of three cell lines. B1 and B7 inhibited proliferation and migration in these cell lines and induced apoptosis in MCF7 and A549 cells. Mechanistic investigations indicated that B1 induces apoptosis in MCF7 cells by inhibiting the AKT signaling pathway and downregulating the expression of apoptosis-related proteins Bcl-2 and Caspase-9.ConclusionNovel Anderson-type POMs B1 (vanadium-centered, methyl-modified) and B7 (vanadium-centered, hydroxyl-modified) exhibited superior efficacy against tumor cells and induced apoptosis via PI3K/AKT pathway, which provides new theoretical avenues for developing POM-mediated antitumor chemotherapeutic medications.
研究领域:
肿瘤学
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药理学
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分子生物学
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无机化学
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转化医学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2016
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IF 3.994
Jinli Li,Xudong Cheng,Yan Chen,Weiming He,Li Ni,Peihua Xiong,Minggang Wei
Luteolin (LUT) is an active agent in cancer prevention and a potential candidate for clinical chemotherapy. However, poor water solubility and extensive excretion have limited the clinical use of luteolin. Herein, we attempted to develop vitamin E d-α-tocopherol acid polyethylene glycol 1000 succinate (TPGS) coated liposomes to improve the accumulation of luteolin in lung cancer. Luteolin or coumarin-6 loaded liposomes were prepared using film-dispersion methods and characterized according to their particle size, polydispersity, zeta potential , and drug encapsulation efficiency. Cellular uptake properties and cytotoxicities of luteolin or coumarin-6 loaded liposomes were determined in A549 cells. Optical in vivo imaging was employed as a method of assessing tumor targeting. The antitumor effect was evaluated in mice xenotransplanted with A549 cancer cells. The results showed that TPGS coated liposomes are spherical, and are ∼176.2 nm in size. TPGS coated liposomes enhanced cellular uptake and apoptosis by upregulating the Bax/Bcl-2 ratio, resulting in improved cytotoxicity in A549 cells. TPGS coated liposomes significantly accumulated in tumor tissue and enhanced tumor inhibition without altering the structures of other organs. Thereby, TPGS coated liposomes provide an effective strategy in cancer chemotherapy for model drugs with poor water solubility such as luteolin.
研究领域:
药剂学
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肿瘤学
·
药物递送系统
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纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2022
·Vol. 23
·期 15
·8380
·
IF 6.208
Zhipeng Dong,Yunxue Yin,Jun Luo,Bingxia Li,Fangning Lou,Qiyan Wang,Qingfa Zhou,Baofen Ye,Yue Wang
Liposome modification by targeting ligands has been used to mediate specific interactions and drug delivery to target cells. In this study, a new peptide ligand, CP7, was found to be able to effectively bind to FGFR1 through reverse molecular docking and could cooperate with VEGFR3 to achieve targeting of A549 cells. CP7 was modified on the surface of the liposome to construct a targeted and safe nanovehicle for the delivery of a therapeutic gene, Mcl-1 siRNA. Due to the specific binding between CP7 and A549 cells, siRNA-loaded liposome-PEG-CP7 showed increased cellular uptake in vitro, resulting in significant apoptosis of tumor cells through silencing of the Mcl-1 gene, which is associated with apoptosis and angiogenesis. This gene delivery system also showed significantly better antitumor activity in tumor-bearing mice in vivo. All of these suggested that siRNA-loaded liposome-PEG-CP7 could be a promising gene drug delivery system with good bioavailability and minimal side effects for treatment.Keywords:CP7;liposome;target delivery;FGFR1;gene drug
研究领域:
药学
·
癌症研究
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分子生物学
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
STAR Protocols
·
2022
·
IF 0
Qingbin Zeng,Qianni Guo,Yaping Yuan,Lei Zhang,Weiping Jiang,Yuqi Yang,Xin Zhou
Summary Due to limited detection sensitivity and contrast limitation, imaging substrates with 129 Xe MRI in living cells is still a challenge. Here, we present an effective protocol to detect and image substrates in human lung cancer cells A549 with hyperpolarized 129 Xe MRI. This protocol was optimized for a cryptophane-based probe sensitive to biothiols and can be expanded to other Xe-based probes to detect potential biomarkers in other mammalian cells. For complete details on the use and execution of this protocol, please refer to Zeng et al. (2021) .
研究领域:
医学成像
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生物医学工程
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分子生物学
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癌症研究
✓ 已验证
DOI
PubMed
Cancer Cell International
·
2020
·Vol. 20
·期 1
·1-16
·
IF 4.175
Zhang Qing,Wu Lian,Liu Shaozheng,Chen Qingjie,Zeng Lingpeng,Chen Xuezhong,Zhang Qing
Background To investigate the efficacy of a PLGA-based nanobody complex in photodynamic therapy (PDT) and NIR-II imaging in A549 tumor hypoxic model.MethodIR1048-MZ was firstly synthesized by conjugating a nitro imidazole group to IR1048. IR1048-MZ and Cat were then encapsulated in PLGA-SH solution. Anti-EGFR-Nanobody was also expressed and purified, and finally Anti-EGFR-Nanobody@PLGA-IR1048MZ-Cat (Nb@IC-NPs) nanobody complex was obtained based on the formation of desulfide bond between PLGA-SH and Anti-EGFR-Nanobody. Size distribution and morphology were characterized by TEM and DLS. Spectrum of Nb@IC-NPs towards NTR was measured by UV and fluorescence, while the particle’s selective response was studied using fluorescence. The uptake of Nb@IC-NPs in A549 cells was observed by flow cytometry and CLSM. In the meantime, its’ catalytic ability that decomposes H2O2 both extra-and intra-cellular was observed by fluorescence and CLSM. In vitro photodynamic toxicity of Nb@IC-NPs was examined by MTT, Live/Dead Cell Staining, Flow Cytometry and Apoptosis Assay. Tumor-bearing model was constructed to observe a semi-quantitative fluorescent distribution and the possibility of NIR-II fluorescence/photoacoustic (PA) imaging. Effect of Nb@IC-NPs on enhancing A549 tumor hypoxia and expression profile of HIF-1α was investigated in the presence of NIR. An A549 tumor metastasis model was also constructed to confirm the complex’ potential to destroy primary tumor, inhibit lung metastasis, and prolong mice’ survival. Lastly, impact of Nb@IC-NPs on mice’ main organs and blood indices was observed.Results Nb@IC-NPs was successfully fabricated with good homogeneity. The fluorescent absorbance of Nb@IC-NPs showed a linear relationship with the concentration of NTR, and a higher concentration of NTR corresponded to a stronger photoacoustic signal. In addition, Nb@IC-NPs showed a stable selectivity toward NTR. Our results also suggested a high efficient uptake of Nb@IC-NPs in A549 cells, which was more efficient than IC-NPs and IR1048-MZ alone. In vitro assays confirmed the effects of Nb@IC-NPs on catalytic O2 generation even in hypoxic cells. The cell viability was upregulated with the nanocomplex at the absence of the laser, whereas it was dramatically declined with laser treatment that excited at 980 nm. Nb@IC-NPs achieved tumor hypoxia NIR-II/PA imaging through assisting A549 gathering. When NIR was applied, Nb@IC-NPs can significantly relieve A549 cellular/tumor hypoxia by generating more reactive oxygen species (ROS), which in turn helps lower the expression level of HIF-1α. In summary, Nb@IC-NPs based PDT can efficiently decimate A549 primary tumor, inhibit metastatic lung cancer, and prolong the lifespan of the mice under tolerable dosage. At last, in vivo toxicity tests of the nanocomplex showed its biosafety to the main organs and normal blood indices values.Conclusion Nb@IC-NPs improves tumor hypoxia through catalytic reaction and lowers the expression level of HIF-1α. It achieves tumor PA imaging through intensified NIR-II fluorescence signal that caused by response of the complex to the lesion’s nitroreductase (NTR). Nb@IC-NPs based PDT can efficiently kill A549 primary tumor, inhibit a lung metastasis, as well as prolong mice’ survival cycle.
研究领域:
癌症研究
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生物医学工程
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药学
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分子生物学
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成像科学
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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）