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JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION · 2024 · IF 3.6

Fabrication of co-delivery liposomal formulation incorporating carmustine and cabazitaxel displays improved cytotoxic potential and induced apoptosis in ovarian cancer cells

Jianming Gong,Renqian Feng,Xiaoqing Fu,Qi Lin,Bicheng Wu

Ovarian cancer is the primary cause of death from cancer in female patients. The existing treatments for ovarian cancer are restricted and ineffective in achieving a cure for the disease. To address this issue, we provide a novel approach to treating ovarian cancer by utilizing a liposomal carrier that effectively delivers the chemotherapeutic drugs carmustine (BCNU) and cabazitaxel (CTX). Initially, the combined impact of BCNU and CTX was confirmed, revealing that this impact reaches its maximum at a ratio of 1:2 mol/mol (BCNU/CTX). After that, the BC-Lipo co-delivery system was developed, which has a high capability for loading drugs (97.48% ± 1.14 for BCNU, 86.29% ± 3.03 for CTX). This system also has a sustained release profile and a beneficial long-circulating feature. The accumulation of BC-Lipo in tumors was dramatically enhanced compared to the accumulation of the free drug. Furthermore, BC-Lipo demonstrated similar levels of cytotoxicity to free BCNU and CTX (BCNU/CTX) when tested on HeLa cells in an in vitro model. Biochemical staining methods investigated the cancer cell’s morphological examination. The apoptosis was confirmed by FITC-Annexin-V/PI staining by flow cytometry analysis. In addition, the investigation of fluorescence and protein markers examined the apoptosis mechanistic pathway, and the results indicated that BC-Lipo induced apoptosis due to mitochondrial membrane potential variation. This proof-of-concept study has established the probability of these BCNU-CTX combined treatments as active drug delivery nanocarriers for poorly soluble BCNU and CTX.

CAS / MDL: 183133-96-2
研究领域: 肿瘤学 · 药剂学 · 纳米技术 · 细胞生物学
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RSC Advances · 2017 ·Vol. 7 ·期 46 ·28637-28646 · IF 3.108

A multianalyte fluorescent carbon dots sensing system constructed based on specific recognition of Fe(III) ions

Pei Song,Lisha Zhang,Hao Long,Meng Meng,Ting Liu,Yongmei Yin,Rimo Xi

In this research, we developed a multianalyte fluorescence sensing system through a carbon dots (CDs)-based fluorescent probe that can specifically recognize Fe(III) by fluorescence quenching. The CDs prepared using black tea by a hydrothermal method show outstanding properties like low cytotoxicity, high photostability, excellent biocompatibility, and high sensitivity. It was found that the fluorescence of CDs can be quenched by micromolar concentrations of Fe(III) in both aqueous solutions as well as living cells. It is well known that glucose can be oxidized by glucose oxidase (GOx) to release H2O2, which, in turn, can oxidize Fe(II) to Fe(III). Based on this consideration, a multianalyte sensing system was established. Therefore the quantitative analysis of Fe(III), H2O2, and glucose with detection limits of 0.25 μM, 0.82 μM, and 1.71 μM, respectively, was achieved by the simple and cost-effective multianalyte CDs sensing system constructed. The sensing system showed high photostability and negligible cytotoxicity toward HeLa cells, which enables it to be applied in the visualization of Fe(III) or H2O2 in living cells. The system was further applied in the detection of Fe(III) or glucose in human serum, and satisfactory results were obtained.

研究领域: 分析化学 · 材料科学 · 生物化学 · 生物医学工程
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Nanoscale · 2022 ·Vol. 14 ·期 39 ·14645-14660 · IF 8.307

Nuclear-targeted carbon quantum dot mediated CRISPR/Cas9 delivery for fluorescence visualization and efficient editing

Li-Min Zhai,Yan Zhao,Rui-Lin Xiao,Shi-Quan Zhang,Bao-Hua Tian,Xin-Xin Li,Rong Zhang,Ri-Sheng Ma,Hai-Xia Liang

Nuclear targeted delivery has great potential in improving the efficiency of non-viral carrier mediated genome editing. However, direct and efficient delivery of CRISPR/Cas9 plasmid into the nucleus remains a challenge. In this study, a nuclear targeted gene delivery platform based on fluorescent carbon quantum dots (CQDs) was developed. Polyethylenimine (PEI) and polyethylene glycol (PEG) synergistically passivated the surface of CQDs, providing an excitation-independent green-emitting fluorescent CQDs–PEI–PEG conjugate (CQDs–PP) with an ultra-small size and positive surface charge. Here we show that CQDs–PP could bind CRISPR/Cas9 plasmid to form a nano-complex by electrostatic attraction, which can bypass lysosomes and enter the nucleus by passive diffusion, and thereby improve the transfection efficiency. Also, CQDs–PP could deliver CRISPR/Cas9 plasmid into HeLa cells, resulting in the insertion/deletion mutation of the target EFHD1 gene. More importantly, CQDs–PP exhibited a considerably higher gene editing efficiency as well as comparable or lower cytotoxicity relative to Lipo2000 and PEI-passivated CQDs–PEI (CQDs–P). Thus, the nuclear-targeted CQDs–PP is expected to constitute an efficient CRISPR/Cas9 delivery carrier in vitro with imaging-trackable ability.

研究领域: 遗传学 · 分子生物学 · 生物医学工程 · 纳米技术
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BIOMACROMOLECULES · 2013 · IF 5.371

Construction of Targeting-Clickable and Tumor-Cleavable Polyurethane Nanomicelles for Multifunctional Intracellular Drug Delivery

Nijia Song,Mingming Ding,Zhicheng Pan,Jiehua Li,Lijuan Zhou,Hong Tan,Qiang Fu

New strategies for the construction of versatile nanovehicles to overcome the multiple challenges of targeted delivery are urgently needed for cancer therapy. To address these needs, we developed a novel targeting-clickable and tumor-cleavable polyurethane nanomicelle for multifunctional delivery of antitumor drugs. The polyurethane was synthesized from biodegradable poly(ε-caprolactone) (PCL) and l-lysine ethyl ester diisocyanate (LDI), further extended by a new designed l-cystine-derivatized chain extender bearing a redox-responsive disulfide bond and clickable alkynyl groups (Cys-PA), and finally terminated by a detachable methoxyl-poly(ethylene glycol) with a highly pH-sensitive benzoic-imine linkage (BPEG). The obtained polymers show attractive self-assembly characteristics and stimuli-responsiveness, good cytocompatibility, and high loading capacity for doxorubicin (DOX). Furthermore, folic acid (FA) as a model targeting ligand was conjugated to the polyurethane micelles via an efficient click reaction. The decoration of FA results in an enhanced cellular uptake and improved drug efficacy toward FA-receptor positive HeLa cancer cells in vitro. As a proof-of-concept, this work provides a facile approach to the design of extracellularly activatable nanocarriers for tumor-targeted and programmed intracellular drug delivery.

研究领域: 药学 · 生物医学工程 · 肿瘤学
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SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY · 2019 · IF 2.931

A phenanthro[9,10-d]imidazole-based AIE active fluorescence probe for sequential detection of Ag+/AgNPs and SCN− in water and saliva samples and its application in living cells

Fanqiang Bu,Bing Zhao,Wei Kan,Liyan Wang,Bo Song,Jianxin Wang,Zhe Zhang,Qigang Deng,Guangming Yin

Ag + and SCN − play extremely important roles in the fields of the physiology and environment. In this work, on the basis of phenanthro[9,10- d ]imidazole derivative ( DIPIP ) which can exhibit the aggregation-induced emission (AIE) properties in aqueous solution, we achieved a sequential on-off-on switch for Ag + and SCN − with high selectivity and sensitivity. A remarkable fluorescence quenching effect of Ag + on the probe DIPIP was observed with 1:2 stoichiometry , Subsequently, the fluorescence intensity of in situ generated DIPIP -Ag + ensemble was easily switched on after the interaction between Ag + and SCN − , which was attributed to the stronger affinity of SCN − to capture Ag + . In particular, the extreme limits of detection (LOD) for Ag + and SCN − in standard solutions were as low as to be 74.5 nM and 7.8 nM, respectively. Furthermore, the probe DIPIP and the DIPIP -Ag + ensemble could be used to detect Ag + in the real water and SCN − in smoker saliva samples, respectively. In addition, the sequential “on-off-on” fluorescence mode of DIPIP to Ag + and SCN − were also successfully applied in living HeLa cells.

CAS / MDL: 623-27-8
研究领域: 分析化学 · 环境科学 · 生物化学 · 细胞生物学
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Molecular Medicine Reports · 2014 ·Vol. 10 ·期 2 ·731-736 · IF 1.484

Combination of aloe-emodin with radiation enhances radiation effects and improves differentiation in human cervical cancer cells

Jinghua Luo,Yong Yuan,Pengyu Chang,Dawei Li,Zhiqiang Liu,Yaqin Qu

The aim of the present study was to investigate the effects of aloe-emodin (AE) on the radiosensitivity and differentiation of HeLa human cervical cancer cells. Cell proliferation was assessed in the HeLa cervical cancer cell line by a methylthiazolyldiphenyl-tetrazolium bromide assay. Radiosensitivity was determined by a colony‑forming assay. Flow cytometry was used for analysis of cell cycle distribution and apoptosis. The expression of γ-H2AX and cyclin B was assessed by western blotting. Alkaline phosphatase (ALP) activity was measured by an ALP activity kit. It was demonstrated that AE inhibited the proliferation of HeLa cells in a concentration- and time-dependent manner, induced G2/M and S phase cell cycle arrest and enhanced the radiosensitivity of HeLa cells. The combination of AE and radiation induced apoptosis, upregulated cyclin B and γ-H2AX expression and further improved ALP activity compared with treatment with AE or radiation alone. AE enhanced the radiosensitivity of HeLa human cervical cancer cells in vitro, inhibited the proliferation of HeLa cells, induced G2/M phase cell cycle arrest and, in combination with radiation, induced the apoptosis and improved the differentiation of HeLa cells.

研究领域: 肿瘤学 · 放射生物学 · 药理学 · 分子生物学
✓ 已验证 DOI PubMed 高影响因子
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EXPERIMENTAL PARASITOLOGY · 2016 · IF 1.623

Antiparasitic effects of oxymatrine and matrine against Toxoplasma gondii in vitro and in vivo

Xiaochuan Zhang,Lili Jin,Zhe Cui,Changhao Zhang,Xue Wu,Hyun Park,Hongmei Quan,Chunmei Jin

Toxoplasma gondii ( T . gondii ) is an important pathogen which can causes serious public health problems. Since the current therapeutic drugs for toxoplasmosis present serious host toxicity, research on effective and new substances of relatively low toxicity is urgently needed. This study was carried out to evaluate the anti-parasitic effect of oxymatrine (OM) and matrine (ME) against T . gondii in vitro and in vivo . In our study, the anti- T . gondii activities of ME and OM were evaluated in vitro using cell counting kit-8 assay, morphological observation and trypan blue exclusion assay. In vivo , mice were sacrificed four days post-infection and ascites were drawn out to determine the extent of tachyzoite proliferation. Viscera indexes and liver biochemical parameters, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutathione (GSH) and malondialdehyde (MDA), were examined to evaluate the toxicity of compounds to mice. As a result, OM and ME showed anti- T . gondii activity but low selectivity toxicity to HeLa cells. Both compounds also significantly decreased the number of tachyzoites in peritoneal cavity and recovered the levels of ALT, AST, GSH and MDA in liver. Moreover, the mice treated with OM or ME achieved better results in viscera index and survival rate than that of spiramycin. These results suggest that OM and ME are likely the sources of new drugs for toxoplasmosis, and further studies will be necessary to compare the efficacy of drug combination, as well as identify its action of mechanism.

CAS / MDL: 8025-81-8
研究领域: 寄生虫学 · 药理学 · 传染病学
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MACROMOLECULAR RESEARCH · 2021 ·Vol. 29 ·期 7 ·453-461 · IF 2.227

Fabrication of Stiffness Gradient Nanocomposite Hydrogels for Mimicking Cell Microenvironment

Hu Yan,Yang Yang,Tian Fei,Xu Pingping,Du Rongcheng,Xia Xuehuan,Xu Shimei

It has attracted much attention to develop a gradient hydrogel for real mimic of the extracellular matrix. Despite simplicity and ease of electrophoresis preparation method, some drawbacks limit the application of the method including toxic organic crosslinker residual, specific ionic monomer types, as well as narrow gradient gaps. In this work, we successfully prepared gradiently crosslinked nonionic PNIPAm/Laponite nanocomposite (NC) hydrogels with controllable gradient structures by adjusting the intensity of the direct current electric field. The results showed that the stiffness, surface property and thermosensitivity of the hydrogel changed with gradient distributions of Laponite. The average stiffness gradients varied from 0.18 kPa/mm, 0.41 kPa/mm to 1.28 kPa/mm by simply adjusting the intensity of the direct current electric field from 0.13 V/mm, 0.20 V/mm to 0.27 V/mm accordingly. The stiffness reached in a range of 13.8∼33.0 kPa. The growth behaviors of human cervical cancer cells (HeLa cells) on the gradient NC hydrogel surface were discussed. Spreading and proliferation, as well as morphology of HeLa cells were closely related to the stiffness of the gradient NC hydrogels. This work develops a stiffness-controllable gradient NC hydrogel and opens up a new insight into the better understanding of cells behaviors in different tissues and organs in vivo .

CAS / MDL: 7727-21-1 110-18-9
研究领域: 材料科学 · 生物医学工程 · 细胞生物学
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Frontiers in Pharmacology · 2022 · IF 5.988

Synthesis and Antitumor Activity of Erlotinib Derivatives Linked With 1,2,3-Triazole.

Peng Deng,Ge Sun,Jie Zhao,Kaitai Yao,Miaomiao Yuan,Lizeng Peng,Longfei Mao

Cervical cancer is one of the most important cause of cancer-related death and presents a major public health problem in many countries. To search for more novel antitumor agents against cervical cancer, 14 erlotinib-linked 1,2,3-triazole compounds were designed, synthesized, and evaluated for their anti-tumor activity. The compounds were confirmed by 1H NMR, 13C NMR, and high-resolution mass spectra (HR MS). Antitumor activity assay results indicated that six of those compounds have remarkable inhibitory activity against human cervical cancer HeLa cells in vitro, among which compound 4m was the most potent with IC50 of 3.79 μM, and compounds 4k, 4i, 4l, 4d, and 4n also demonstrated remarkable antitumor activity with IC50 of 3.79, 4.16, 4.36, 7.02, and 8.21 μM. We found three of the most potent compounds 4d, 4k, and 4l induced potent apoptosis and cell cycle arrest in HeLa cells, and compounds 4d and 4l significantly restrained the cell colony formation and showed moderate epidermal growth factor receptor (EGFR) inhibitory activity with IC50 of 13.01 and 1.76 μM. Therefore, these experiments indicate that these erlotinib-linked 1,2,3-triazole compounds are potential to act as effective anticancer agents against cervical cancer.Keywords: EGFR, erlotinib, 1,2,3-triazole, HeLa, antitumor activity

研究领域: 肿瘤学 · 药物化学 · 药理学
✓ 已验证 DOI PubMed 高影响因子
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MICROCHEMICAL JOURNAL · 2025 · IF 5.1

A sandwiched PEDOT@Pt-based antifouling electrochemical sensor for real-time monitoring of cells cultured in three-dimensional hydrogel

Xue-Bo Hu,Yi-Peng Zhang,Zi-He Jin,Yi-Xiao Zhang,Yu-Ling Wang,Xiao-Long Fu,Jun-Tao Cao,Yan-Ming Liu

Three-dimensional cell culture has been considered as a powerful tool to achieve the in-vitro investigation that can mimics the cell behaviors and functions in body. With the advancement on this field, the requirements on applying effective identification and quantification strategy for real-time monitoring of cells are becoming more urgently. Therefore, we developed a PEDOT@Pt-based antifouling electrochemical sensor and collagen hydrogel integrated 3D platform. Among the 3D platform, the PEDOT@Pt-based electrochemical sensor presented high performance toward reactive oxygen species (hydrogen peroxide), with a high sensitivity of 176.0 nA/μM in the linear range of 100 nM to 100 μM, and a low detection limit of 43.1 nM. Besides, under the simulated cell culture environment, the electrochemical performance retained up to 70.8 % of the original performance, demonstrating good antifouling property. As a proof of concept, the A549 and HeLa cells were cultured into the 3D platform and the real-time monitoring of cell-released reactive oxygen species were further conducted. More importantly, the reactive oxygen species release behavior of cells under different stimulation were also explored within the 3D integrated platform, which is expected to enable precise biochemical analysis of cells under the in vivo -like microenvironment.

研究领域: 生物传感器 · 电化学 · 细胞生物学 · 生物工程 · 分析化学
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MACROMOLECULAR RESEARCH · 2022 ·Vol. 30 ·期 4 ·238-244 · IF 2.127

Oxidized Alginate Hydrogel-Based Derivatives with Optimized Features for Cell Culture Scaffold

Twizeyimana Etienne,Zhang Shuang,Mukerabigwi Jean Felix,Ge Zhishen

Advances in designing smart hydrogels with the structures and properties similar to the interior of extracellular matrix have aroused the interest of researchers as promising cell support scaffolds in the field of tissue engineering. In this study, a novel hydrogel system is developed from natural polysaccharides that are sodium alginate, gelatin and carboxymethyl chitosan through Schiff base cross-linking mechanism. By mixing these three components, the hydrogel system with tunable strength and gelation time was obtained and abbreviated as oxACG hydrogel. Moreover, the obtained hydrogels are biocompatible and can sustain the growth and proliferation of Hela cells after 24 h incubation. The experimental results show that the hydrogel possesses a relatively short gelation time that is around 3 min, high gel strength and negligible cell cytotoxicity. The oxACG hydrogel composite exhibited desirable properties, and they can be used as high-performance multifunctional injectable hydrogels in cell therapy.

研究领域: 材料科学 · 生物材料 · 组织工程 · 细胞生物学
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ULTRASONICS SONOCHEMISTRY · 2018 · IF 6.012

IR780 loaded perfluorohexane nanodroplets for efficient sonodynamic effect induced by short-pulsed focused ultrasound

Nan Chang,Dui Qin,Pengying Wu,Shanshan Xu,Supin Wang,Mingxi Wan

Inertial cavitation is crucial for the therapeutic effects of sonodynamic. Therefore, approaches that can induce highly efficient inertial cavitation should be of benefit for sonodynamic effect. Our previous study demonstrated that highly efficient inertial cavitation activity can be achieved through the combinatorial use of a short-pulsed focused ultrasound (SPFU) sequence and perfluorohexane (PFH) nanodroplets. Herein, we applied the SPFU sequence and PFH nanodroplets in sonodynamic. A hydrophobic sonosensitizer, IR780 iodine, was loaded inside denatured bovine serum albumin-shelled PFH (PFH@BSA-IR780) nanodroplets. The sonodynamic efficacy was validated by treating HeLa cervical cancer cells. Under SPFU exposure, PFH@BSA-IR780 nanodroplets were highly effective in promoting reactive oxygen species generation and inducing cancer cell death. A significant decrease in cell viability was achieved within just 10 s. Besides the cytotoxicity of ROS, the mechanical bioeffects of inertial cavitation also led to severe cell death resulting from higher acoustic power or the longer treatment time. The application of the SPFU sequence coupled with PFH@BSA-IR780 nanodroplets is a promising strategy for efficient sonodynamic.

研究领域: 医学物理 · 癌症治疗 · 超声治疗 · 纳米技术
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