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Materials Science & Engineering C-Materials for Biological Applications · 2019 · IF 4.959

Cancer-targeted and intracellular delivery of Bcl-2-converting peptide with functional macroporous silica nanoparticles for biosafe treatment

Yuehuang Wu,Pengjin Ge,Weixia Xu,Mingyu Li,Qi Kang,Xiaokun Zhang,Jingjing Xie

Therapeutic peptide, NuBCP-9 (N9) as a Bcl-2 functional converter, has been demonstrated to have the remarkable anticancer efficiency in Bcl-2-abundant cancer. However, it faced technical challenges in clinical use, such as the low bioavailability, the easily-destroyed bio-stability, and the insusceptibility to cellular interior. With the potential of mesoporous silica nanoparticles (MSNs) as the promising delivery vehicle of therapeutic macromolecules, we developed a kind of MSNs with the surface coating of folic acid (FA) for cancer cell targeting and with the macropore loading of N9 peptide for cancer therapy. Our results showed that the functional MSNs had the relatively greater biosafety than the naked MSNs in zebrafish models, leading to less than 30% embryo of death at 200 μg/ml, which could further specifically target the folate receptor (FR)-overexpressed cervical cancer HeLa cells instead of FR-negative normal embryonic kidney HEK 293T cells in a FA-competitive manner. N9 peptide with the delivery of functional MSNs could be internalized by HeLa cells, and co-localized with mitochondria in a Bcl-2-dependent manner. Moreover, N9 peptide delivered by FA-modified MSNs displayed the excellent anticancer efficiency with great selectivity, inducing approximately 52% HeLa cells into apoptosis. In summary, our results illustrated the potential of functional MSNs with large pore size as an efficient nanocarrier for the intracellular delivery of peptide drugs with targeting proteins to realize cancer therapy.

CAS / MDL: 102-71-6
研究领域: 纳米技术 · 癌症治疗 · 药物递送系统 · 分子生物学 · 生物医学工程
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OPTICAL MATERIALS · 2023 · IF 3.9

Red emission upconversion of NaYF4: Yb3+/Er3+ nanoparticles: Rapid preparation via single-mode focused microwave method and their application in cell imaging

Chunyang Kang,Xianwei Zuo,Lei Zhao,Cuiling Ren,Yan Wang,Yidan Liu,Xin He,Xin Li,Genliang Han

The red emission of upconversion nanoparticles (UCNPs) is located in an “optical window” range of the biological tissue, which has a promising prospect in biology application. In this work, novel red-emitting NaYF 4 :Yb 3+ /Er 3+ UCNPs with CH 3 COO − modifications were synthesized by single-mode focused microwave method. The morphology, structure, and luminescence properties of as-prepared UCNPs were characterized. The results showed that single-mode focused microwave method was an effective approach to prepare hydrophilic and strongly red emission UCNPs within a drastically reduced reaction time (only 10 min) compared to the traditional methods. Importantly, we also demonstrated that the CH 3 COO − modified NaYF 4 :Yb 3+ /Er 3+ UCNPs could be successfully applied for in vitro imaging of HeLa cells. This work not only provides a rapidly synthetic methodology for the preparation of red-emitting UCNPs but also offers an effective material for cancer cell imaging .

CAS / MDL: 207234-04-6
研究领域: 材料科学 · 纳米技术 · 生物医学工程 · 细胞生物学
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SENSORS AND ACTUATORS B-CHEMICAL · 2022 · IF 9.221

Imaging the dynamic processes of hydrogen sulfide using a rapid “turn-on” mitochondria-targeting fluorescent probe

Kai Wang,Xue Yang,Meng-Ya Guo,Xu-Yang Chen,Ting Li,Ru Yan,Yu-Shun Yang,Hai-Liang Zhu,Zhi-Gang Hu

Hydrogen sulfide (H 2 S) is a signal molecule that is significantly involved in cell protection, vascular regulation, and neuro-transmission. Nevertheless, abnormal levels of H 2 S are intimately relevant to Alzheimer’s disease, liver cirrhosis, diabetes mellitus, and Down syndrome. To improve the H 2 S detection in vitro and in vivo , we developed RDM-H 2 S , a novel red-emission fluorescent probe . RDM-H 2 S has a rapid response (120 s), high sensitivity (LOD = 310 nM), obvious response degree (234 folds), relatively long excitation/emission wavelength (565 nm/620 nm), and steady emission in pH 6–9. In addition, RDM-H 2 S showed high specificity to H 2 S in various species. Due to the low cytotoxicity of RDM-H 2 S , it was beneficial to the application of biological depth imaging . In addition, RDM-H 2 S could measure exogenous and endogenous H 2 S in distinct biological models, such as HeLa cells and zebrafish. Besides, RDM-H 2 S had excellent mitochondrial targeting ability and could be used to monitor H 2 S in living mice. RDM-H 2 S could visualize endogenous H 2 S in different tissues and 4T1-xenograft tumor mice. Additionally, RDM-H 2 S also exhibited immense application potential for the visualization of H 2 S in the process of inflammation. RDM-H 2 S was applied for measuring the level of H 2 S in human plasma samples. Consequently, RDM-H 2 S was determined to be a valuable tool for monitoring H 2 S in pre-clinical diagnosis.

研究领域: 生物化学 · 医学诊断 · 分子生物学
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SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY · 2025 · IF 4.6

Mitochondria-immobilized fluorescent probes for viscosity and cellular imaging

Lingchen Wang,Wenqiang Song,Fengxia Li,Shaomin Shuang,Shengmei Song,Yunfeng Yang,Yue Huang,Kun Wang

A mitochondria-immobilized fluorescent probe Mito-CDM was designed and synthesized for viscosity sensing via the twisted intramolecular charge transfer (TICT) mechanism. The N , N -diethylaminophenyl group is the viscosity-sensitive unit in the prepared Mito-CDM molecular structure, while the pyridinium cation is the mitochondria-targeting group that is responsible for monitoring mitochondrial viscosity. As the viscosity increased from 0.55 cp (0% glycerol) to 950 cp (100% glycerol), the fluorescence intensity of Mito-CDM at 586 nm enhanced gradually and there is a good linear relationship between fluorescence intensity and viscosity ( n  = 11, R 2  = 0.9957). In high-viscosity media, Mito-CDM exhibits a 166-fold fluorescence enhancement at 586 nm. It is crucial to note that the benzyl chloride group has the ability to react with highly reactive thiols on mitochondrial proteins, which enables Mito-CDM to be immobilized on mitochondria for extended periods. Additionally, Mito-CDM was successfully used to monitor mitochondrial viscosity changes during nystatin and lipopolysaccharide-induced inflammation in HeLa cells.

研究领域: 生物化学 · 细胞生物学 · 分析化学 · 生物物理 · 分子成像
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NANO · 2024 · IF 1

Hyaluronic Acid-Modified Hollow Glass Beads Used for Cell Sorting with High Efficiency

Minghao Zhang,Weidi Lin,Nana Li,Kuanjie Ma,Qing Zhang,Xinyi Ma,Zhen Liu,Yurong Cai

It is of great significance to sort specific types of cells through a fast and efficient technology in biomedical research and clinical applications. In this study, commercial hollow glass beads were modified with 3-aminopropyltriethoxysilane (ATPES) and hyaluronic acid (HA) sequentially, which can capture HeLa cells with nearly 100% efficiency within 10 min. The beads can specifically recognize and sort HeLa cells from a cell coculture of HeLa and L-929 depending on their strong buoyancy and good affinity with cancer cells. The job provides a facile, quick and low-cost cell sorting method, which has potential application in the fields of specific and efficient cell isolation.

研究领域: 生物医学工程 · 细胞生物学 · 癌症研究 · 生物材料 · 芯片实验室技术
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JOURNAL OF NANOPARTICLE RESEARCH · 2014 ·Vol. 16 ·期 8 ·1-11 · IF 2.278

PEGylated graphene oxide as a nanocarrier for podophyllotoxin

Zhu Shaojia,Zhen Hong,Li Yongjun,Wang Ping,Huang Xiaoyu,Shi Ping

Graphene, a two-dimensional nanomaterial, has become a hot spot of research at the interface of nanotechnology and biomedicine. In this study, the oxidized form of graphene, graphene oxide (GO), was functionalized with 6-armed polyethylene glycol (PEG), which rendered it stable and biocompatible in physiological solution. The successful synthesis of PEGylated graphene oxide (GO-PEG) nanocarrier with low toxicity was confirmed by UV–Vis spectroscopy, Fourier-transform infrared spectroscopy, atomic force microscopy, and thermogravimetric analysis. By dynamic light scattering (DLS), the size distribution of the nanoparticles were shown to be 60–200 nm. Furthermore, a complex by loading an aromatic anticancer compound, podophyllotoxin (PPT), onto GO-PEG (GO-PEG/PPT) via π – π stacking and hydrophobic interactions was investigated. It was demonstrated that GO-PEG/PPT showed remarkably high cytotoxicity compared to free PPT in both the human cervical adenocarcinoma HeLa cell line and human hepatoma SMMC-7721 cell line. The loading and delivery of anticancer drugs using this kind of graphene-based nanocarrier may find potential application in biomedicine.

CAS / MDL: 3326-32-7
研究领域: 纳米技术 · 生物医学工程 · 药学 · 癌症研究
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BIOSENSORS & BIOELECTRONICS · 2014 · IF 6.451

PEI/Zr4+-coated nanopore for selective and sensitive detection of ATP in combination with single-walled carbon nanotubes

Siqi Zhang,Amin Bao,Ting Sun,Erkang Wang,Jiahai Wang

By virtue of a biomimetic nanopore and single-walled carbon nanotubes, a new sensor for adenosine triphosphate (ATP) detection is designed. As compared to the routine approach, the present scenario does not entail the surface modification of nanopore with analyte-specific probes. The underlying mechanism relies on a symmetric nanopore sequentially modified with polyethyleneimine (PEI) and Zr 4+ that can quantitate the concentration of ATP-bound aptamer, while other free aptamers are removed by single-walled carbon nanotubes (SWNTs). The detection limit of the nanopore sensor is 27.46   nM, and the linear range is from 50   nM to 400   nM. The biosensor with an excellent selectivity against guanosine triphosphate (GTP), uridine triphosphate (UTP), and cytosine triphosphate (CTP) can be applied in the real samples such as Hela cell .

CAS / MDL: 7585-20-8 77-86-1
研究领域: 纳米技术 · 生物传感 · 分析化学 · 生物技术
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Journal of Materials Chemistry B · 2021 ·Vol. 9 ·期 15 ·3326-3334 · IF 6.331

Molecular design of peptide amphiphiles for controlled self-assembly and drug release

Ziqi Liu,Xuan Tang,Feng Feng,Jing Xu,Can Wu,Guoru Dai,Wanqing Yue,Wenying Zhong,Keming Xu

Peptide amphiphile-based supramolecular hydrogels hold great promise in drug delivery applications. To cater for a specific drug dose in a demanding biomedical scenario, sophisticated design of peptide amphiphile (PA) molecules is required to tune their self-assembling behaviours as well as drug releasing profiles. Herein, we designed a series of PAs with various capping groups and C-terminal amino acids to systematically optimize their self-assembling capabilities for controlled drug release. First, we evaluated the influence of N-terminal capping groups to find that the 2-naphthylacetyl moiety (Nap) greatly assisted hydrogelation of PAs. Next, self-assembling behaviours of Nap-capped PAs were compared among three candidates that bore varying hydrophilic moieties at the C-terminus (Nap-C12-VVAAG, Nap-C12-VVAAD and Nap-C12-VVAADD, denoted as 1-G, 1-D, and 1-DD). It was found that 1-G and 1-D co-assembled with doxorubicin (DOX) and calcium ions (Ca2+) at a higher efficiency than 1-DD, for 1-G/Ca2+/DOX and 1-D/Ca2+/DOX hydrogels displayed a dense nanofibrillar network, with lower minimal gelation concentrations and greater storage modulus values. Interestingly, these PA/Ca2+/DOX hydrogels exhibited tunable release rates of DOX in vitro, with fast release of DOX found in 1-DD/Ca2+/DOX and slow release in 1-G/Ca2+/DOX and 1-D/Ca2+/DOX. Further cell experiments demonstrated that 1-G/Ca2+/DOX and 1-D/Ca2+/DOX exhibited higher inhibitory efficacy against HeLa cells, as compared to DOX solution and 1-DD/Ca2+/DOX. Finally, PA/Ca2+/DOX hydrogels displayed a longer retention time of DOX than aqueous DOX solution in animal experiments, and sustained release of DOX from hydrogels was also evidenced by slow and persisting accumulation of DOX in the major organs of hydrogel-treated mice.

研究领域: 材料科学 · 药剂学 · 生物医学工程 · 药物递送系统
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Marine Drugs · 2020 ·Vol. 18 ·期 7 ·375 · IF 4.073

12-Deacetyl-12-epi-Scalaradial, a Scalarane Sesterterpenoid from a Marine Sponge Hippospongia sp., Induces HeLa Cells Apoptosis via MAPK/ERK Pathway and Modulates Nuclear Receptor Nur77

Mi Zhou,Bo-Rong Peng,Wenjing Tian,Jui-Hsin Su,Guanghui Wang,Ting Lin,Dequan Zeng,Jyh-Horng Sheu,Haifeng Chen

12-Deacetyl-12-epi-scalaradial, a scalarane sesterterpenoid from a marine spongeHippospongia sp, has been reported to possess cytotoxic activity on HepG2, MCF-7, and HCT-116 cells. However, there is no research to indicate that 12-deacetyl-12-epi-scalaradial exhibited anticancer effect on cervical cancer HeLa cells. The aim of this study was to investigate the anticancer activity of 12-deacetyl-12-epi-scalaradial against HeLa cells and to explore the mechanism. The results from a methylthiazolyldiphenyl-tetrazolium (MTT) assay suggested that 12-deacetyl-12-epi-scalaradial suppressed the proliferation of HeLa cells and flow cytometry analysis showed 12-deacetyl-12-epi-scalaradial could induce the apoptosis of HeLa cells in dose- and time-dependent manner. Western blotting analysis demonstrated that 12-deacetyl-12-epi-scalaradial triggered apoptosis via mediating the extrinsic pathway and was found to suppress MAPK/ERK pathway which was associate with cancer cell death. Nur77, a critical number of orphan nuclear receptors, plays diverse roles in tumor development as a transcription factor and has been considered as a promising anticancer drug target. The dual-luciferase reporter assays suggested that 12-deacetyl-12-epi-scalaradial could selectively enhance the trans-activation activity of Nur77. Furthermore, Western blotting analysis and fluorescence quenching showed that 12-deacetyl-12-epi-scalaradial could induce the phosphorylation of Nur77 and interact with the ligand-binding domain (LBD) of Nur77. Our research confirmed 12-deacetyl-12-epi-scalaradial as a potential agent for cervical cancer therapy and provided a view that 12-deacetyl-12-epi-scalaradial may be a modulator of Nur77.Keywords:12-deacetyl-12-epi-scalaradial;HeLa cells;apoptosis;Nur77;MAPK/ERK pathway

CAS / MDL: 298-93-1
研究领域: 海洋化学 · 癌症研究 · 分子生物学 · 药理学
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NEW JOURNAL OF CHEMISTRY · 2018 ·Vol. 42 ·期 16 ·13479-13485 · IF 3.201

Imaging of lysosomal pH changes with a novel quinoline/benzothiazole probe

Li Fan,Ming Nan,Jinyin Ge,Xiaodong Wang,Bo Lin,Wenjia Zhang,Shaomin Shuang,Chuan Dong

A novel quinoline/benzothiazole pH probe (E)-2-(2-(quinolin-4-yl)vinyl)benzothiazole (BTVQ) was facilely synthesized. BTVQ exhibits remarkable emission response to pH and can image pH changes within the extreme acidity range of 3.0–3.8 with a pKa of 3.52. Moreover, BTVQ displays a notably large Stokes shift of 110 nm, which can reduce the excitation interference. BTVQ was successfully applied in HeLa cells and E. coli cells, suggesting that BTVQ can be employed as one of the few lysosome specific probes for imaging acidic intracellular pH changes, especially under extreme-acidity conditions in bacteria.

CAS / MDL: 120-75-2 4363-93-3
研究领域: 化学 · 细胞生物学 · 生物成像
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PHARMAZIE · 2021 ·Vol. 76 ·期 10 ·503-506 · IF 1.267

DCLK1 might be a therapeutic target of osthole against cervical cancer

Pan Liuliu,Zhang Xiaodan,Wang Danhan,Huang Min,Huang Qiusui,Duan Ping,Mei Jie

Discovering compounds with anti-cervical cancer effect and clarifying their targets will help promoting the precise treatment of cervical cancer. The present study intended to clarify the effect of osthole on cervical cancer cells, and to explore the possibility of DCLK1 as its target. Annexin V-PE staining and flow cytometry methods were used to determine cell apoptosis. Meanwhile, apoptosis related biomarkers were probed by immunoblotting. The MTT assay was employed to study the effect of osthole in combined with or without LRRK2-IN-1 (a DCLK1 inhibitor) on cell proliferation. Then, combination index was determined. To examine the interaction of osthole with DCLK1, molecular docking was carried out. Based on the biological database from cBioPortal, the association between DCLK1 and clinical manifestations of cervical cancer were evaluated. The results showed that osthole can significantly induce apoptosis of HeLa and Me-180. When combined with LRRK2-IN-1, the effect of osthole on cell proliferation was antagonized, suggesting that it might competitive binding to DCLK1. Furthermore, molecular docking showed that osthole interacts with Val468 residues of DCLK1 to form hydrogen bonds. The analysis of database showed that DCLK1 frequently mutant and deleted in cervical cancer, and is related to cell survival, tumor progression and recurrence. However, no obvious correlations were found between DCLK1 and lymphatic metastasis/differentiation. In conclusion, osthole significantly inhibits the survival of cervical cancer cells. It's probably target DCLK1 mechanistically via interacting with Val468. DCLK1 could be a potential therapeutic target for cervical cancer.

CAS / MDL: 484-12-8
研究领域: 肿瘤学 · 药理学 · 分子生物学 · 癌症研究
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Pharmaceutics · 2025 ·Vol. 17 ·期 2 ·206 · IF 5.5

Dual pH- and Temperature-Responsive Performance and Cytotoxicity of N-Isopropylacrylamide and Acrylic Acid Functionalized Bimodal Mesoporous Silicas with Core–Shell Structure and Fluorescent Feature for Hela Cell

Huijie Ge,Xiaoli Wang,Shiyang Bai,Yuhua Bi,Fei Liu,Jihong Sun,Wenliang Fu,Donggang Xu

Background:Polymer-coated mesoporous silica nanoparticles have attracted immense research interest in stimuli-responsive drug delivery systems due to their drug-releasing ability on demand at specific sites in response to external or internal signals. However, the relationships between the coated-copolymer encapsulation and drug delivery performance in the hybrid nanocomposites was rarely reported. Therefore, the main objectives of the present work are to explore the cell uptake, cellular internalization, cytotoxicity, and hemolysis performance of the fluorescent hybrid materials with different polymer-encapsulated amounts.Methods:Using (2-(2-aminoethyl)-6-(dimethylamino)-1H-benzo[de]isoquinoline-1,3(2H)-dione)-doped poly[(N-isopropylacrylamide)-co-(acrylic acid)] (PAN) as a shell and bimodal mesoporous silicas (BMMs) as a core, the dual pH- and temperature-responsive mesoporous PAN@M-BMMs with the fluorescent performances were synthesized via a radical polymerization approach. The effects of the PAN-coated thicknesses on their physicochemical properties and structural features were demonstrated via XRD and SAXS patterns, SEM and TEM images, FT-IR spectra, and TG analysis. Their mass fractal (Dm) evolutions were elucidated on the basis of the SAXS patterns and fluorescence spectra.Results:TheDmvalues increased from 2.74 to 2.87 with an increase of the PAN-coated amount from 17 to 26.5% along with the particle size from 76.1 to 85.6 nm and blue-shifting of their fluorescent emission wavelength from 470 to 444 nm. Meanwhile, the PAN@M-BMMs exhibited a high ibuprofen (IBU) loading capacity (13.8%) and strong dual pH-/temperature-responsive drug-releasing performances (83.1%) at pH 7.4 and 25 °C, as comparison with that (17.9%) at pH 2.0 and 37 °C. The simulated results confirmed that the adsorption energy decreased from −67.18 kJ/mol for pure BMMs to −116.76 kJ/mol for PAN@M-BMMs, indicating the PAN-grafting on the surfaces of the BMMs core was beneficial to improve its IBU-adsorption capacity. Its uptake in the HeLa cell line was performed via microplate readers, confocal microscopy, flow cytometry, and ICP measurement, showing a low cytotoxicity at a concentration up to 100 µg/mL. Specially, P0.2AN@M-BMMs had a superior cellular uptake and fluorescence properties via the time-dependent uptake experiments, and exhibited the highest silicon content via the cellular internalization analysis, as compared to other carriers. Hemolysis tests confirmed the hemolysis rates below 5%.Conclusions:These demonstrations verified that PAN@M-BMMs should be a promising biomedical application prospect.

研究领域: 材料科学 · 生物医学工程 · 药物递送系统
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