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MATERIALS SCIENCE FORUM · 2011 · IF 0

The Difference between Rare Earth Ions and Alkaline Earth Metal Ions in DNA Condensation Process

Jun Zhang,Xiao Ting Shi,Wei Guo,Zhong Zhang,Hong Yang

The structural transition of DNA double-stranded induced by Ce3+ or Mg2+ ions was investigated in this paper. By atomic force microscopy, different types of condensed DNA structures were observed at the presence of Ce3+ or Mg2+ ions. The results show that there are some differences between rare earth ions and alkaline earth metal ions in the DNA condensation process.

研究领域: 生物化学 · 分子生物学 · 纳米技术
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EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY · 2017 · IF 4.519

Rigid aromatic linking moiety in cationic lipids for enhanced gene transfection efficiency

Bing Wang,Rui-Mo Zhao,Ji Zhang,Yan-Hong Liu,Zheng Huang,Qing-Ying Yu,Xiao-Qi Yu

Although numerous cationic lipids have been developed as non-viral gene vectors , the structure-activity relationship (SAR) of these materials remains unclear and needs further investigation. In this work, a series of lysine-derived cationic lipids containing linkages with different rigidity were designed and synthesized. SAR studies showed that lipids with rigid aromatic linkage could promote the formation of tight liposomes and enhance DNA condensation, which is essential for the gene delivery process. These lipids could give much higher transfection efficiency than those containing more flexible aliphatic linkage in various cell lines. Moreover, the rigid aromatic linkage also affords the material higher serum tolerance ability. Flow cytometry assay revealed that the target lipids have good cellular uptake, while confocal microscopy observation showed weaker endosome escape than Lipofectamine 2000. To solve such problem and further increase the transfection efficiency, some lysosomotropic reagents were used to improve the endosome escape of lipoplex. As expected, higher transfection efficiency than Lipofectamine 2000 could be obtained via this strategy. Cytotoxicity assay showed that these lipids have lower toxicity in various cell lines than Lipofectamine 2000, suggesting their potential for further application. This work demonstrates that a rigid aromatic linkage might distinctly improve the gene transfection abilities of cationic lipids and affords information to construct safe and efficient gene vector towards practical application.

研究领域: 分子生物学 · 基因治疗 · 药物递送系统
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COLLOIDS AND SURFACES B-BIOINTERFACES · 2014 · IF 4.287

Promoting DNA loading on magnetic nanoparticles using a DNA condensation strategy

Zhi Shan,Youjun Jiang,Mengyu Guo,J. Craig Bennett,Xianghai Li,Hefeng Tian,Ken Oakes,Xu Zhang,Yi Zhou,Qianming Huang,Huaping Chen

Maximizing DNA loading on magnetic nanoparticles (MNPs) is crucial for their successful utilization in gene transfer, DNA isolation, and bio-analytical applications. This enhancement is typically achieved by altering particle size and surfaces as well as charge density and ionic strength. We demonstrate a novel route for promoting DNA loading on amino-modified silica-coated magnetic nanoparticles (ASMNPs) by prior condensation of elongated DNA to a compact globule before adsorption. The enhanced DNA-loading capacity, as demonstrated by a reduction in the number of ASMNPs needed to achieve complexation, was presumably due to the elimination of DNA wrapping around nanoparticles and substantially reduced electrostatic interactions of DNA with nanoparticles because the compacted DNA globule conformation decreases its exposed surface charge. The maximum loading capacity of ASMNPs for condensed DNA was 4.4 times greater than that for elongated coiled DNA, achieving the highest ever reported value of 385   μg   mg −1 . Practical applications for plasmid DNA isolation from cleared lysate confirmed the reliability of the proposed method.

CAS / MDL: 919-30-2 25322-68-3
研究领域: 生物化学 · 纳米生物学 · 分子生物学
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FOOD AND CHEMICAL TOXICOLOGY · 2018 · IF 3.977

Apios americana Medik flowers extract protects PC12 cells against H2O2 induced neurotoxicity via regulating autophagy

Qiang Chu,Lushuang Yu,Zihuan Zheng,Meng Chen,Zheng Hua,Miaojia Hang,Yonglu Li,Xixi Li,Yangyang Liu,Yunyun Yang,Xiaodong Zheng

Since flavonoids are antioxidant compounds, they could beneficially affect neurodegenerative diseases where reactive oxygen species are involved. In this study, we firstly isolated and identified fourteen compounds from the flowers of Apios americana Medik. Then, we tested whether Apios americana Medik flowers water extract (AFWE) exerts a protective effect on H 2 O 2 induced PC12 cells injure. As expected, pretreatment with AFWE inhibited cytotoxicity and DNA condensation in H 2 O 2 induced PC12 cells. Exposure of PC12 cells to H 2 O 2 resulted in reactive oxygen species accumulation and mitochondrial dysfunction, while AFWE alleviated these damages. AFWE obviously reversed the alternations as H2O2 increased Caspase-3 and decreased the ratio of Bcl-2/Bax expressions. Furthermore, autophagy in PC12 cells was further activated by AFWE, which was beneficial to resisting adversity. These results manifest that AFWE prevents H 2 O 2 induced damage via regulating autophagy.

研究领域: 神经科学 · 药理学 · 细胞生物学 · 生物化学
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ACS Applied Bio Materials · 2019 · IF 0

Integument of Cytoplasmic Membrane onto Cationic DNA Condensates for Selective Gene Expression at Homologous Cells

Hongyan Cui,Jing Xia,Liuwei Zhang,Ming Qian,Hao Wang,Jingyun Wang,Qixian Chen

The surface properties of drug/gene delivery systems are critical important to their ultimate therapeutic performance. In the present studies, cytoplasmic membranes deriving from cancerous cells (Hep-G2) were attempted as the external integument onto the polycationic theranostic DNA delivery systems with the aim of diminishing unfavorable biointerfacial reactions of nanomedicine. Herein, a multiple of polycationic oligoethylenimine (OEI) segments were installed onto the surface of luminescent carbon quantum dots (CQD, facile bioimaging utilities) for complexation with plasmid DNA (pDNA) into DNA delivery constructs, followed by surface integument by cytoplasmic membranes. The subsequent investigations verified this strategic integument capable of shielding the unfavorable surface positive net charge of the polycationic DNA delivery constructs and thereby markedly diminishing the potential nonspecific reactions in biological milieu. Leadingly, improved biocompatibilities as well as additional protection of inner vulnerable DNA cargos from enzymatic degradation, have been accomplished. More importantly, preferential affinities to the homologous cells were identified as a result of this membrane integument based on facile fluorescence quantification for the intracellular CQD. Significant higher cellular uptake efficiency for the polycationic constructs based on Hep-G2 membrane integument was confirmed in the homologous Hep-G2 cells in contrast to the heterologous MCF-7 and HeLa cells (approximately 4-fold). Note that this homologous privilege was observed for the delivery constructs not only from cancerous HeLa and MCF-7 membrane integuments but also normal cells (COS-7), heralding the intriguing potentials of this membrane-integument strategy in pursuit of targeting functions. Eventually, gene expression activities were also determined to prevail in the homologous cells. Therefore, our proposed surface integument strategy by homologous cell membrane could imply an alternative facile and versatile avenue in construction of active-targeted nanomedicine.

CAS / MDL: 6066-82-6
研究领域: 分子生物学 · 纳米医学 · 基因工程 · 癌症研究 · 药物递送系统
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Scientific Reports · 2017 ·Vol. 7 ·期 1 ·1-10 · IF 4.259

An easy gene assembling strategy for light-promoted transfection by combining host-guest interaction of cucurbit[7]uril and gold nanoparticles

Du Jianwei,Zhang Peng,Zhao Xiao,Wang Youxiang

Cucurbit[7]uril (CB[7]), a representative member of the host family cucurbit[n]uril, can host-guest interact with many guest molecules such as adamantane, viologen and naphthalene derivatives. This host-guest interaction provides an easy strategy in gene vector assembling. Furthermore, CB[7] can self-assemble on gold nanospheres (AuNSs). Herein, the combination of CB[7] and AuNSs provides both advantages of host-guest interaction and photo-thermal effect of AuNSs. In this study, polyethyleneimine (PEI) and polyethylene glycol (PEG) were separately interacted with CB[7] via host-guest interaction. Then by assembling on AuNSs, PEI and PEG were combined together to condense DNA into polyplexes as well as enhance circulation stability of the polyplexes. These gene vectors were found to have high cellular uptake efficiency and low cytotoxicity. Furthermore, the well distributed AuNSs in the polyplexes could transform light into heat under light exposure because of the photo-thermal effect. This was found to effectively promote the entry of gene into cytoplasm and highly enhanced gene transfection efficiency.

研究领域: 纳米技术 · 分子生物学 · 基因治疗 · 材料科学
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COLLOIDS AND SURFACES B-BIOINTERFACES · 2015 · IF 4.152

Induction of apoptosis in cancer cells through N-acetyl-l-leucine-modified polyethylenimine-mediated p53 gene delivery

Zhiyuan Li,Liu Zhang,Quanshun Li

Herein, N -acetyl- l -leucine-modified polyethylenimine was successfully constructed through the EDC/NHS-mediated coupling reaction and employed as vectors to accomplish p53 gene delivery using HeLa (p53wt) and PC-3 cells (p53null) as models. Compared with PEI25K, the derivatives exhibited lower cytotoxicity, protein adsorption and hemolytic activity, together with satisfactory pDNA condensation capability and gene transfection efficiency. After p53 transfection, MTT analysis confirmed that the cell proliferation was inhibited. Flow cytometric analysis showed that the derivative-mediated p53 delivery could induce stronger early apoptosis than PEI25K and Lipofectamine 2000 . Further, PC-3 cells showed higher sensitivity to the exogenous p53 transfection than HeLa cells. The mechanism for inducing apoptosis was determined to be up-regulation of p53 expression at both mRNA and protein levels using RT-PCR and western blotting analysis. Expression level and activity analysis of caspase-3, -8 and -9, and mitochondrial membrane potential measurement revealed that p53 transfection mediated by these derivatives facilitated early apoptosis of tumor cells via a mitochondria-dependent apoptosis pathway. Thus, the derivatives showed potential as biocompatible carriers for realizing effective tumor gene therapy.

研究领域: 癌症生物学 · 分子生物学 · 基因治疗 · 药学
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