RSC Advances
·
2015
·Vol. 5
·期 128
·105901-105907
·
IF 3.84
Guan-Hai Wang,Hui-Kang Yang,Yi Zhao,Da-Wei Zhang,Li-Ming Zhang,Jian-Tao Lin
In this work, novel biodegradable cationic micelles were prepared based on poly-(N-ε-carbobenzyloxy-L-lysine) (PZLL) and chitosan (CS) by click reaction, and applied for co-delivery of doxorubicin (DOX) and p53 plasmid. The structure of the copolymer was characterized by 1H NMR and FTIR. The loading amount of DOX in the micelles was 12.8%. Fluorescence spectra confirmed that DOX interacted via π–π stacking with micelles when DOX was encapsulated into the micelles. In particular, its complexation with plasmid DNA was investigated using agarose gel electrophoresis, flow cytometry, zeta potential, and particle size analyses as well as transmission electron microscopy observations. The results showed that the copolymers have a strong pDNA condensation ability and provide protection of pDNA against deoxyribonuclease I degradation. CS-g-PZLL/DOX/p53 nanoparticles showed good gene transfection efficiency in vitro. Fluorescence images and flow cytometry tests revealed that p53 and DOX could be efficiently transported into Hela tumor cells simultaneously, and the optimum N/P ratio for p53 transfection was 20/1. For co-delivery analysis, the obtained CS-g-PZLL/DOX/p53 complexes showed a better inhibitory effect on Hela tumor cells than DOX or p53 used singly.
研究领域:
药剂学
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肿瘤学
·
生物材料学
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DOI
高影响因子
NEW JOURNAL OF CHEMISTRY
·
2024
·Vol. 48
·期 36
·15782-15789
·
IF 2.7
Hongling Tao,Yanyue Chen,Jiawen Liu,Jiali Liu,Yunhui Yang,Rong Hu
p53 gene is one of the most important anticancer genes and has been recognized as a typical biomarker for the early diagnosis of cancers. In this paper, a portable point-of-care testing (POCT) platform was developed for the colorimetric and photothermal dual-modal analysis of the p53 gene. Long concatemer G4 structures with high catalytic activity were formed by a target-driven hybridization chain reaction, and their catalytic properties can further be enhanced with the help of iodide ions. This dual-modal method realized the sensitive multicolor visual point-of-care detection of the p53 gene, where color variations from colourless to blue were easily distinguished by the naked eye. The temperature output was achieved by effective photothermal conversion and regulation guided by the accumulated concatemer G4 complexes in the TMB–H2O2 system, avoiding the need for complex instruments. The proposed dual-modal assay for p53 gene detection is cost-effective, simple, highly sensitive (3.34 pM), stable, and remarkably selective. It was also applied to determine the concentration of the p53 gene in spiked serum samples.
研究领域:
分子生物学
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癌症诊断
·
生物化学
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DOI
高影响因子
BIOSENSORS & BIOELECTRONICS
·
2015
·
IF 6.409
Zonghua Wang,Jianfei Xia,Daimin Song,Feifei Zhang,Min Yang,Rijun Gui,Lin Xia,Sai Bi,Yanzhi Xia
A versatile label-free quadruple signal amplification biosensing platform for p53 gene (target DNA) detection was proposed. The chitosan–graphene (CS–GR) modified electrode with excellent electron transfer ability could provide a large specific surface for high levels of AuNPs-DNA attachment. The large amount of AuNPs could immobilize more capture probes and enhance the electrochemical signal with the excellent electrocatalytic activity . Furthermore, with the assist of N.BstNB I (the nicking endonuclease), target DNA could be reused and more G-quadruplex-hemin DNAzyme could be formed, allowing significant signal amplification in the presence of H 2 O 2 . Such strategy can enhance the oxidation–reduction reaction of adsorbed methylene blue (MB) and efficiently improve the sensitivity of the proposed biosensor. The morphologies of materials and the stepwise biosensor were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM) and cyclic voltammetry (CV). Differential pulse voltammetry (DPV) signals of MB provided quantitative measures of the concentrations of target DNA, with a linear calibration range of 1.0×10 −15 –1.0×10 −9 M and a detection limit of 3.0×10 −16 M. Moreover, the resulting biosensor also exhibited good specificity, acceptable reproducibility and stability, indicating that the present strategy was promising for broad potential application in clinic assay.
研究领域:
生物化学
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医学检测
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纳米材料科学
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DOI
PubMed
高影响因子
ANNALS OF BIOMEDICAL ENGINEERING
·
2016
·Vol. 44
·期 11
·3372-3383
·
IF 2.887
Xie Bei,Peng Jian,Wang Shuo,Zhang Xing,Nie Hemin
The combination of gene therapy and chemotherapy has showed increased therapeutic efficacy in the treatment of cancers, but it is not well investigated about the actual coordination pattern between therapeutic gene and chemical drug. In this work, p53/BPEI-β-CD/AD-dox complex was fabricated and employed to investigate the interaction manner between p53 and doxorubicin (Dox). Briefly, branched polyethylenimine (BPEI) was conjugated with β-cyclodextrin hydrate (β-CD) to form BPEI-β-CD backbone, and p53 plasmid was condensed by positively charged BPEI via electrostatic interaction, while Dox was first conjugated with adamantine (AD) and then assembled with BPEI-β-CD backbone via the host–guest interaction. It was found that the BPEI-β-CD backbone possessed high endocytosis efficiency but low cytotoxicity. Moreover, p53/BPEI-β-CD/AD-dox complex released Dox and enabled the expression of p53 gene in a sequential manner, and the released Dox and expressed p53 gene showed successive inhibition of the growth of HeLa cells in vitro . With the ability to co-deliver chemical drug and therapeutic gene and exert their inhibitory actions on tumor cell growth in a sequential manner, this DNA/BPEI-β-CD/AD-drug complex via electrostatic interaction and host–guest assembly not only achieved long-term efficacy in inhibiting tumor cell growth but also can be employed as a platform to investigate the coordination pattern between chemical drugs and therapeutic genes for other purposes.
研究领域:
生物医学
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肿瘤学
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药物递送
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2022
·
IF 6.51
Zhou Fang,Min Zhang,Rui Kang,Mingxiao Cui,Mengdi Song,Kehai Liu
Gene therapy is a superior therapeutic means in cancer therapy. However, the instability of nucleic acid and the lack of suitable delivery carrier greatly restricts its further development and application. Herein, we coupled low molecular weight polyethyleneimine (LMW PEI) through disulfide bonds , then modified it with manganese dioxide (MnO 2 ) nanosheets and nuclear localization signal peptide (NLS), as a p53 gene carrier, and finally coated it with B16F10 cell membrane to construct a novel gene-carrier system [email protected] 2 -PEI-NLS-ss/p53 ( [email protected] /p53). Tumor cell membrane coating endows nanoparticles with homotypic targeting and immune escape capabilities, disulfide-crosslinked LMW-PEI has high transfection efficiency and low toxicity, and NLS peptides enhance nuclear delivery and improve p53 gene delivery efficiency; meanwhile, MnO 2 nanosheets oxidize high intracellular concentration of glutathione (GSH), sensitizing p53 gene-mediated antitumor therapy. The results showed that the novel biofilm-camouflaged [email protected] /p53 nanoparticles had a highly specific targeting effect on homologous cancer cells and could effectively inhibit tumor growth in vitro and in vivo . Besides, MnO 2 loading improved p53-mediated tumor regression . This novel gene delivery platform is of great significance in improving gene delivery efficiency and enhancing anti-tumor therapy.
研究领域:
生物医学工程
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癌症研究
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分子生物学
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产品关联
DOI
PubMed
高影响因子
NEW JOURNAL OF CHEMISTRY
·
2018
·Vol. 42
·期 16
·13375-13381
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IF 3.201
Haobo Han,Wenqi Chen,Jiebing Yang,Jiayuan Zhang,Quanshun Li,Yan Yang
The modification of 2-amino-6-chloropurine on polyamidoamine was performed to synthesize a derivative, AP-PAMAM, which was then employed as a carrier for p53 gene delivery to achieve anti-tumor efficacy. Using a human prostate tumor cell line PC-3 as a model, enhanced expression level of p53 gene could be detected by RT-PCR, qPCR and western blotting. Based on the successful p53 gene transfection, an obvious anti-proliferative effect could be obtained, which was identified to be associated with the simultaneous induction of cell apoptosis and cell cycle arrest at the G1 phase. The cell apoptosis was elucidated to be triggered by the activation of the mitochondria-dependent apoptotic signaling pathway. In addition, AP-PAMAM/p53 transfection could restrain the migration of tumor cells as demonstrated by wound healing and Transwell migration assays. Notably, AP-PAMAM-mediated p53 delivery exhibited a stronger inhibitory effect on both cell proliferation and migration than the PAMAM/p53 group. In summary, AP-PAMAM/p53 transfection provided a promising route to achieve the p53-based gene therapy.
研究领域:
分子生物学
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肿瘤学
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药剂学
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产品关联
DOI
高影响因子
RSC Advances
·
2018
·Vol. 8
·期 45
·25611-25616
·
IF 2.936
Dan Han,Chunying Wei
In this paper, we construct a fluorescence nucleic acid probe based on DNA-templated silver nanoclusters (DNA-Ag NCs) for the detection of the p53 gene. The fluorescence biosensing of the “turn-on” model is successfully implemented as a result of the target-triggered configurational change in the hairpin DNA probe and the synthesis of fluorescent Ag NCs. With this biosensor, the limit of detection (LOD) for the p53 gene is 3.57 nM and the linear range is 250–2500 nM in phosphate buffer solution, while a LOD of 6.06 nM in the linear range of 250–2500 nM is obtained in 1% diluted fetal calf serum. So this probe, with its advantages of specificity, practical application, easy operation and low cost, will have favourable development prospects in biological sensing and imaging.
研究领域:
生物化学
·
分子生物学
·
纳米生物学
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产品关联
DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2021
·
IF 7.46
Jiaying Zhao,Danqun Huo,Xintong Geng,Jing Bao,Jingzhou Hou,Zhengfan Shui,Huisi Yang,Yanli Qi,Yian Hu,Mei Yang,Changjun Hou
p53 gene is one of the most important anticancer genes and has been recognized as a typical biomarker for the early diagnosis, classification, and prognosis evaluation of cancers. In this work, a novel biosensing strategy integrating MoS 2 -AuNPs modified carbon paper (CP) conductive substrate and enzyme signal amplification technique was developed for p53 gene detection. We constructed an immobilized DNA S1 probe and a biotinylated DNA S3 probe, which could induce the formation of an S1-p53-S3 DNA sandwich complex in the presence of target sequence p53. After conjugating avidin-HRP via biotin-avidin reaction, 3,3’,5,5’-tetramethylbenzidine would be catalyzed for signal amplification in the presence of H 2 O 2 so that the induced electrochemical response would change with proportional to the abundance of p53 gene. The proposed biosensor exhibited two linearities in the range of 1.0 × 10 −15 ∼ 1.0 × 10 -12 M and 1.0 × 10 -12 ∼ 1.0 × 10 -6 M, and the limit of detection (LOD) was 68 fM. No significant interferences were observed during detecting real serum samples. Moreover, it is worth pointing out that the biosensor together with its disposable, low-cost, and stable features can discriminate well between the mutated and wild type p53 gene extracted from tumor cells (wtTP53 in MCF-7 and mutated in SK-BR-3), demonstrating a promising applicability for clinical test.
研究领域:
生物传感器
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癌症诊断
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纳米技术
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电化学
·
分子生物学
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DOI
高影响因子
MOLECULAR PHARMACEUTICS
·
2014
·
IF 4.787
Xuefang Ding,Wei Wang,Yazhe Wang,Xiuli Bao,Yu Wang,Cheng Wang,Jian Chen,Fangrong Zhang,Jianping Zhou
The study is aimed to develop a versatile reticular polyethylenimine (PEI) derivative eprosartan-g-PEI (ESP) conjugate-mediated targeted drug and gene codelivery system for tumor therapy. Eprosartan (ES), an angiotensin II type 1 receptor blocker (ARB), which has been proven to exert beneficial effects on tumor progression, vascularization, and metastasis as the conventional antihypertensive drug, was conjugated with PEI-1.8K chains into ESP via a bis-amide bond of pH-sensitivity to overcome high cytotoxicity and nontargeted gene delivery of PEI-25K. P53 gene was encapsulated in the ESP to form the codelivery system of ESP/p53 complexes, and this system was comprehensively characterized. In vitro ESP/p53 complexes had a significant effect on inhibiting angiogenesis by reducing the expression and secretion of VEGF. In vivo the effective antitumor activity of ESP/p53 complexes was observed on nude mice bearing PANC-1 xenografts, and the microvessel density (MVD) examination demonstrated that ESP/p53 complex-produced antitumor efficacy was closely correlated with the efficient angiogenesis repression. These findings disclosed that the multifunctional ESP/p53 complexes might be a promising dual anticancer drug and gene codelivery system.
研究领域:
药理学
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肿瘤学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF THE ELECTROCHEMICAL SOCIETY
·
2020
·Vol. 167
·期 2
·027535
·
IF 3.721
Qian Bi,Xiaoyan Gan,Ruo Yuan,Yun Xiang
Herein, a new signal amplification strategy on the basis of copper-free click chemistry-mediated cyclic ligation of DNA for detecting cancer-related mutant p53 (mp53) gene with high sensitivity is described. The complementary sandwich hybridization of the target mp53 gene with the azide-modified capture probes and the dibenzocyclooctyne-conjugated and G-quadruplex containing signal probes pulls the azide and dibenzocyclooctyne moieties into close proximity, leading to copper-free click ligation of the signal probes on the sensor surface. Subsequent thermal recycling of the target gene results in the attachment of lots of signal probes on the electrode. The many G-quadruplex segments in the signal probes then bind and confine hemin within the vicinity of the electrode surface, thereby yielding substantially amplified reduction current response for detecting the mutant target mp53 sequences with a low detection limit of 7.7 fM. This sensor can also discriminate mutant and wild gene with single base mutation and can realize target gene detection in diluted human serums. Distinct from conventional copper-mediated click chemistry and ligase-based DNA ligation, our approach is copper- and enzyme-free, making our method a simple and robust signal amplification sensing means for detecting low levels of different DNA biomarkers.
研究领域:
生物化学
·
分子生物学
·
医学诊断
✓ 已验证
产品关联
DOI
高影响因子
PHARMACEUTICAL DEVELOPMENT AND TECHNOLOGY
·
2022
·
IF 3.915
Qingfa Guo,Fanyuan Kong,Xiaoru Pan,Shuhua Cao
Recent findings revealed that low-concentration paclitaxel(DTX) could enhance cytotoxicity by upregulating p53 expression in lung cancer cell lines. So, co-delivery of DTX and RFP-p53 gene with PEA nanoparticles (NPs) was studied. The prepared DTX loaded PEA NPs (PEA/DTX) were characterized by particle size distribution, morphology, zeta potential, and crystallography and cytotoxicity. Results showed that the PEA/DTX NPs had a mall particle size (≤100 nm), moderate zeta potential (≥40 mV) and drug loading of 9.0%, DTX was released from PEA/DTX NPs in an extended period in vitro. More important, agarose gel electrophoresis showed that PEA/DTX cationic NPs were able to completely bind RFP-p53 gene with mean particles size and zeta potential. Studies on cellular uptake of (PEA/DTX)/RFP-p53 NPs demonstrated that both drug and gene were effectively taken up by A549 tumor cells. It was found that intravenous injection of (PEA/DTX)/RFP-p53 NPs efficiently inhibited growth of subcutaneous A549 carcinoma in vivo (p < 0.05) and was significantly less side effect than that of mice treated with the other groups. Therefore, the (PEA/DTX)/RFP-p53 NPs might be a promising candidate for A549 cancer therapy.
研究领域:
药剂学
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肿瘤学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF MATERIALS SCIENCE & TECHNOLOGY
·
2017
·
IF 2.764
Bei Xie,Jipeng Yi,Jian Peng,Xing Zhang,Lei Lei,Dapeng Zhao,Zhixin Lei,Hemin Nie
Co-delivery of chemical drugs and therapeutic genes for synergistic therapy provides a promising strategy to treat devastating diseases. However, the real-time coordination patterns between chemical drugs and therapeutic genes remain poorly understood. Herein, the complexes of doxorubicin/graphene oxide-polyethyleneimine/p53 plasmid (Dox/GO-PEI/p53) were fabricated and employed to investigate the synergistic manner between Dox and p53 in the inhibition of HeLa cell growth. GO was conjugated with PEI to form the GO-PEI backbone as the delivery vector. The GO backbone provided surfaces with a high specific area to load Dox via the π-π stacking interaction, and was able to release Dox significantly faster at pH 5.0 than at pH 7.0, while the positively charged PEI section of GO-PEI could condense plasmids into GO-PEI/DNA nanoparticles via the electrostatic interaction . The nanoparticles efficiently mediated the transfection of DNA in HeLa cells, with lower cytotoxicity compared to PEI/DNA nanoparticles. Furthermore, the complexes of Dox/GO-PEI/p53 released Dox and expressed p53 gene in a sequential manner, and showed successive inhibition of the in vitro growth of HeLa cells. This type of drug/GO-PEI/DNA complex can be employed as a platform to investigate the coordination pattern between chemical drugs and therapeutic genes for tumor therapy.
研究领域:
生物医学工程
·
肿瘤学
·
分子生物学
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）