TALANTA
·
2018
·
IF 4.244
Kailun Deng,Lei Wang,Qi Xia,Ruiyuan Liu,Jinqing Qu
Nucleus imaging is of great importance for understanding cellular processes of genetic expression, proliferation and growth, etc. Although many nucleic-acid selective dyes for nucleus staining are available, few of them meet multiple standards. Herein, we report a cationic fluorescence dye FTI that possesses visible light excitation (436 nm), orange emission (571 nm) and a large Stokes shift (~135 nm) for nucleic-acid staining. FTI displays an obvious and sensitive fluorescent response to DNA in vitro with a 6.4-fold quantum yield increasing. Co-staining and nucleic acid digest experiments in live cells demonstrate that FTI exhibits an unexpected selectivity for the nucleolus of the cells due to the stronger affinity to RNA than DNA. Because of good photostability and low cytotoxicity, FTI can accomplish a promising stain for DNA recognition in vitro and nucleolus-specific imaging in cancer cells.
研究领域:
细胞生物学
·
分子生物学
·
生物成像
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2016
·
IF 8.387
Hui Xiong,Shi Du,Jiang Ni,Jianping Zhou,Jing Yao
Dual-targeted nanoparticles have been increasingly used to realize greater anti-proliferation effect by attacking double key sites of tumor cells. In order to retain nuclei inhibition effect and enhance DOX-induced apoptosis by mitochondrial pathway simultaneously, hyaluronic acid (HA) modified hydroxyapatite (HAP) nanoparticles (HAP-HA), the functional calcium-based tumor targeting nanoparticles, have been developed. In this nanosystem , HA acts as an active tumor-targeting ligand to bind the CD44 receptors which are overexpressed on the surface of tumor cells while HAP can load and deliver DOX to both nuclei and mitochondria of tumor cells. In this study, DOX-loaded HAP-HA nanoparticles (DOX/HAP-HA) exhibited satisfactory drug loading efficiency which was up to 214.55 ± 51.05 μg mg −1 and showed a uniform nano-scaled particle size. The mitochondrial and nuclei targetability of DOX/HAP-HA was confirmed by confocal laser scanning microscopy analyses. Besides, western blot assay demonstrated that DOX/HAP-HA could markedly enhance mitochondrial cytochrome C leakage and thereby activate apoptotic cascade associated with it. In addition, in vivo anti-tumor efficacy and toxicity evaluation of DOX/HAP-HA indicated that DOX/HAP-HA was more effective and less harmful compared to other groups. DOX/HAP-HA might be a new promising targeted delivery system for effective cancer therapy.
研究领域:
药理学
·
纳米技术
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Polymer Chemistry
·
2016
·Vol. 7
·期 19
·3268-3276
·
IF 5.687
Ye Chen,Leilei Rui,Lichao Liu,Weian Zhang
Supramolecular amphiphiles based on a pillar[5]arene with enhanced photodynamic therapy have been fabricated. Supramolecular amphiphiles based on host–guest complexation between a poly(ethylene glycol)-functionalized pillar[5]arene (PEG-P[5]A) and a pyridinium-terminated porphyrin derivative bearing a disulfide bond (TPPC6-SS-Py) could self-assemble into spherical micelles in aqueous solution with good colloidal stability as confirmed by transmission electron microscopy (TEM) and dynamic light scattering (DLS). Also, PEG-P[5]A/TPPC6-SS-Py micelles exhibited rapid release of porphyrin photosensitizers in a reducing environment. In addition, these micelles demonstrated nearly no toxicity in the dark but a higher photocytotoxicity upon light irradiation evaluated by the MTT assay. Flow cytometry and confocal laser scanning microscopy (CLSM) revealed a more effective cellular uptake property compared with free porphyrin. Therefore, novel reduction-responsive supramolecular amphiphiles with rapid drug release and superior cell internalization ability are constructed, which may provide a platform for drug delivery systems.
研究领域:
生物化学
·
药剂学
·
纳米医学
✓ 已验证
产品关联
DOI
高影响因子
NANOTECHNOLOGY
·
2019
·Vol. 30
·期 35
·355604
·
IF 3.399
Keju Zhang,Dong Zhou,Zhiguo Wang,Yuhong Zhang,Peixin He
The synthesis of drug delivery systems based on surface-modified mesoporous silica hollow structures remains a huge challenge. In this paper, we have obtained hollow mesoporous silica nanoparticles (MSNs) by surfactant directed sol-gel assisted hydrothermal treatment. The MSNs have the inorganic-organic hybrid frameworks with uniform diameter distribution (260 nm), and their specific surface area, mesoporous size and pore volume are 540 m2 g−1, 3.7 nm, 0.58 cm3 g−1, respectively. It was proved that the preparation of hollow ethane-bridged nanospheres with two silicon source was due to the high crosslinking of the silicone interface and hydrothermal treatment, providing a new approach for the study of drug-loaded and controlled release behavior. Based on the synthesis of MSNs, MSNs were modified by methacryloxy propyl trimethoxyl silane (MPS) on the surface of MSNs. Then N-isopropylacryamide (NIPAM) and acrylic acid (AA) were grafted onto the surface of modified MSNs. The hollow ethane-bridged PNA–MSNs (poly (NIPAM-co-acrylic acid)-MSNs) with two silicon source were prepared successfully. Due to their distinctive hollow structure, PNA–MSNs demonstrated high drug encapsulation efficiency (70.4% ± 2.9%). The experiment results proved that the modified hollow nanoparticles not only had good biocompatibility and stability, but also possessed pH-/thermal-dual responsiveness in drug release.
研究领域:
材料科学
·
生物医学工程
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2019
·Vol. 7
·期 10
·4142-4152
·
IF 5.251
Jian-Bin Zhen,Mu-Han Zhao,Ying Ge,Ya Liu,Li-Wei Xu,Cheng Chen,Yong-Kuan Gong,Ke-Wu Yang
The emergence of drug-resistant bacteria poses a serious threat to public health. The traditional antibiotics have specific intracellular targets and disinfect via chemical ways, which easily lead to the development of drug resistance, therefore, cationic peptides as promising antibiotic agents have attracted extensive attention due to their unique properties. Herein, we report a class of amphiphilic peptide-based pectinate polymers with primary amino groups. The polymers spontaneously self-assembled into the positively charged nanoparticles, which were evaluated and confirmed by scanning electron microscopy (SEM) and dynamic light scattering (DLS). Biological assays revealed that the nanoparticles showed broad-spectrum antibacterial efficacy against both Gram-positive and Gram-negative bacteria, exhibiting a MIC of 16 μg mL−1 against six clinical bacteria, namely, E. faecalis, S. aureus, MRSA, VRE, P. aeruginosa, and K. pneumonia, and three bacterial strains E. coli and E. coli producing NDM-1 and ImiS, and showed a sterilization rate of 95.6% and 94.7% on S. aureus and E. coli, respectively. Importantly, the nanoparticles did not result in drug-resistance for both the normal and drug-resistant bacteria tested after 14 passages and showed low toxicity on the mouse fibroblast cells (L929). The fluorescence staining, electrical conductivity, SEM, and surface plasmon resonance (SPR) characterization suggested that the nanoparticles initially bound to the surface of the bacteria, then pierced into the membranes of the bacteria with their phenyl groups, and finally disrupted the membranes, resulting in ions leaking out and thus exhibiting broad-spectrum antibacterial efficacy. This bactericidal mechanism that the nanoparticles employed does not lead the bacteria susceptible to developing drug resistance. This study provides a promising pathway for the development of the efficient antibacterial materials.
研究领域:
生物材料学
·
微生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2019
·
IF 4.213
Xin Jin,Jianping Zhou,Zhenhai Zhang,Huixia Lv
Synergistic combination therapy involving the integration of chemotherapeutics and chemosensitizers into micelles has demonstrated great potential for tumor-specific location release. Here, the natural product betulinic acid (BA) and chemical drug lonidamine (LN) were used as chemosensitizers in combination with doxorubicin (DOX) for ovarian cancer treatment. We designed pH-sensitive peptide derivatives and constructed an all-in-one multifunctional multidrug pH-sensitive targeting delivery system for the synergistic co-delivery of DOX and BA (or LN). The combination of DOX and BA was found to elicit better therapeutic effects and lower cardiotoxicity than the DOX and LN combination in Skvo3 cells. Further, loading DOX/BA into the present micellar systems enabled burst release at the tumor location, leading to enhanced anti-tumor effects and reduced off-target effects. More importantly, DOX/BA micelles elicited fewer adverse effects on cardiac function and leukocyte counts in Skvo3 subcutaneous xenograft models. These features suggest that the designed micelles represent a promising multifunctional strategy for the efficient treatment of ovarian cancer.
研究领域:
药学
·
癌症研究
·
药物递送系统
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMOSPHERE
·
2019
·
IF 5.108
Feng Wei,Jiadong Li,Changchang Dong,Yajun Bi,Xiaojun Han
Photocatalytic disinfection with high performance is thought to be a promising way for water purification . Herein, plasmonic Ag doped urea-derived graphitic carbon nitride (g-C 3 N 4 ) composites were fabricated via in-situ photo-deposition at room temperature as the visible-light photocatalyst. Scan electron microscopy and transmission electron microscopy images showed the uniform dispersion of Ag nanoparticles on the surface of g-C 3 N 4 sheet, which facilitated the synergistic effect of antibacterial performance from Ag and photocatalytic property from Ag/g-C 3 N 4 composites. Photocatalytic water disinfection against Escherichia coli with visible light was performed to demonstrate the improved photocatalytic property with assistance of Ag. The 3-Ag/g-C 3 N 4 exhibited the best bactericidal performance by inactivating all bacteria within 120 min with damaged cell membranes of Escherichia coli observed by scan electron microscopy and transmission electron microscopy images. Photoluminescence spectra, steady-state surface photovoltage spectra, photocurrent response, and electrochemical impedance spectra results revealed that Ag nanoparticles inhibited the recombination of photo-generated e − and h + pairs and further reinforced the photocatalytic performance of g-C 3 N 4 . Scavenger experiments indicated that h + produced on valence band of g-C 3 N 4 dominated the photocatalytic disinfection process against Escherichia coli . This work further proved Ag/g-C 3 N 4 showed great potential in photocatalytic water disinfection under visible-light irradiation.
研究领域:
环境科学
·
材料科学
·
微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2018
·
IF 13.709
Jun Wang,Jinlei Li,Jiani Yu,Hongwu Zhang,Bingbo Zhang
Persistent luminous nanoparticles (PLNPs) have been capturing increasing attention in biomedical imaging because of their long-life emission and concomitant benefits (e.g., zero-autofluorescence background, high signal-to-noise ratio). Although there are quite some synthetic methodologies to synthesize PLNPs, those for constructing functional structured PLNPs remain largely unexplored. Herein we report the design principle, synthesis route, and proof-of-concept applications of hollow structured PLNPs with near-infrared (NIR) persistent luminescence, namely afterglow, and tunable sizes for tumor afterglow imaging and chemical/photodynamic therapies. The design principle leverages on the crystallization of the immobilized parent ions on the purgeable carbon spheres. This strategy provides large and size-tunable hollow cavities to PLNPs after calcination. Building on the hollow cavity of PLNPs, high chemical drug (DOX) or photosensitizer (Si-Pc) loading can be achieved. The DOX/Si-Pc-loaded hollow PLNPs exhibit efficient tumor suppression based on the features of large cavity and afterglow of PLNPs. These hollow structured PLNPs, like traditional solid PLNPs, are quite stable and can be repeatedly activated, and particularly can selectively target tumor lesion, permitting rechargeable afterglow imaging in living mice. Our research supplies a strategy to synthesize hollow structured PLNPs, and hopefully it could inspire other innovative structures for cancer theranostics.
研究领域:
生物医学工程
·
材料科学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanoscale Research Letters
·
2019
·Vol. 14
·期 1
·1-11
·
IF 3.159
Qi Feng,Liu Ruizhen
Integrating multiple tumor therapy functions into one nanoplatform has been a new tumor therapy strategy in recent years. Herein, a dual-modality therapy agent consisting of molybdenum selenide nanodots (MoSe 2 NDs) and bovine serum albumin (BSA) assembled nanospheres (MoSe 2 @BSA NSs) was successfully synthesized. After conjugation of folic acid (FA) molecules via polyethylene glycol (PEG) “bridges,” the FA-MoSe 2 @BSA NSs were equipped with tumor-targeting function. The BSA and PEG modifications provided the unstable MoSe 2 NDs with excellent physiological stability. Since the end-product FA-MoSe 2 @BSA NSs had strong near-infrared (NIR) and X-ray absorbance properties, they exhibited good photothermal properties with excellent photothermal stability and radio-sensitization ability, hence, were explored as photothermal radiotherapy agents. In vitro and in vivo experiments indicated that the FA-MoSe 2 @BSA NSs possessed highly efficient tumor-targeting effect, great biocompability, and synergistic photothermal radiotherapy effect. This work suggests that such biocompatible FA-MoSe 2 @BSA NSs may be a promising multifunctional dual-modality tumor therapy agent for use in combination tumor therapy.
研究领域:
肿瘤治疗
·
生物材料
·
医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CELLULAR SIGNALLING
·
2024
·
IF 4.4
Zheng-Ming Cao,Su Fu,Chao Dong,Teng-Yue Yang,Xiao-Kang Liu,Chun-Lin Zhang,Dong-Zhe Li
The progression of osteoarthritis (OA) includes the initial inflammation, subsequent degradation of the extracellular matrix (ECM), and chondrocyte apoptosis. Down syndrome candidate region 1 (DSCR1) is a stress-responsive gene and expresses in varied types of cells, including chondrocytes. Bioinformatics analysis of GSE103416 and GSE104739 datasets showed higher DSCR1 expression in the inflamed cartilage tissues and chondrocytes of OA. DSCR1 had two major isoforms, isoform 1 (DSCR1–1) and isoform 4 (DSCR1–4). We found that DSCR1–1 had a faster ( in vitro ) and higher expression ( in vivo ) response to OA compared to DSCR1–4. IL-1β-induced apoptosis, inflammation, and ECM degradation in chondrocytes were attenuated by DSCR1–1 overexpression. DSCR1–1 triggered the phosphorylation of cAMP response element-binding 1 (CREB1) at 133 serine sites by decreasing calcineurin activity. Moreover, activated CREB1 moved into the cell nucleus and combined in the promoter regions of aldehyde dehydrogenase 2 (ALDH2), thus enhancing its gene transcription. ALDH2 could recover Wnt/β-catenin signaling transduction by enhancing phosphorylation of β-catenin at 33/37 serine sites and inhibiting the migration of β-catenin protein from the cellular matrix to the nucleus. In vivo , adenoviruses (1 × 10 8 PFU) overexpressing DSCR1–1 were injected into the articular cavity of C57BL/6 mice with medial meniscus surgery-induced OA, and it showed that DSCR1–1 overexpression ameliorated cartilage injury. Collectively, our study demonstrates that DSCR1–1 may be a potential therapeutic target of OA.
研究领域:
骨科
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
·
2024
·
IF 4.6
Haocong Zhang,Liangbi Xiang,Hong Yuan,Hailong Yu
Neuroinflammation-caused secondary injury is a key event after spinal cord injury (SCI). Dedicator of cytokinesis 2 (DOCK2) belonging to DOCK-A subfamily has a vital role in microglia polarization and neuroinflammation via mediating Rac activation. However, the role of DOCK2 in SCI is unclear. In the present study, SCI model in mice was established by an impactor at thoracic T10 level. DOCK2 expression was significantly increased in the spinal cord after SCI. After knocking down DOCK2 using a lentivirus-mediated method, SCI mice exhibited improved motor function recovery, as revealed by increased Basso Mouse Scale (BMS) score, angle of incline, and relatively coordinated footprint, and decreased damaged area in the spinal cord. DOCK2 deficiency reduced neuronal apoptosis in the spinal cord after injury. Besides, deficiency of DOCK2 suppressed neuroinflammation after SCI, demonstrated by the reduction in pro-inflammatory mediators including IFN-γ, IL-1β and IL-6 and the increase in IL-4, IL-10 and IL-13, anti-inflammatory factors. The CD86, iNOS and COX-2 were down-regulated in the spinal cord, whereas CD206, Arg-1 and TGF-β were up-regulated by DOCK2 deficiency. Rac activation was prevented by DOCK2 deficiency following SCI. In vitro experiments were conducted for further verification. Treatment of BV-2 microglia with lentivirus-mediated DOCK2 inhibited IFN-γ/LPS-induced pro-inflammatory microglia polarization but increased IL-4-induced anti-inflammatory microglia, through inhibiting Rac activation. In brief, our data reveal that DOCK2 deficiency improves functional recovery in mice after SCI, which is related to Rac activation.
研究领域:
神经科学
·
免疫学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CANCER GENE THERAPY
·
2023
·
IF 6.4
Liang Yichao,Wu Di,Qu Qiao,Li Zhilong,Yin Hongzhuan
MORC family CW-type zinc finger 4 (MORC4) possessing nuclear matrix binding domains has been observed to be involved in multiple cancer development. By digging three gene expression omnibus (GEO) gene microarrays (GSE110223, GSE110224 and GSE24514), we found that MORC4 was overexpressed in colorectal cancer (CRC) samples (log 2 Fold change >1, p < 0.05). We aimed to investigate the role of MORC4 in CRC malignant behaviors, with an emphasis on polycomb group ring finger 1 (PCGF1)/cyclin-dependent kinase inhibitor 1A (CDKN1A) axis. Firstly, we confirmed MORC4 as an upregulated gene in 60 pairs of frozen CRC and adjacent normal samples. MORC4 overexpression increased proliferation and metastasis, and decreased apoptosis in SW480 and HT29 cells, which was diminished by the knockdown of PCGF1, a transcriptional repressor of CDKN1A (a potent cyclin-dependent kinase inhibitor). MORC4 was further identified as a novel molecule that interacted with PCGF1 via coimmunoprecipitation. MORC4 itself did not substantially suppress CDKN1A transcriptional activity, but it augmented PCGF1’s effect on CDKN1A. Additionally, MORC4 acted as the substrate of HECT, C2, and WW domain-containing E3 ubiquitin protein ligase 2 (HECW2) and was degraded through ubiquitin-proteasome system. Collectively, our work suggested that MORC4 accelerated CRC progression via governing PCGF1/CDKN1A signaling.
研究领域:
肿瘤学
·
分子生物学
·
癌症遗传学
✓ 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）