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NEW JOURNAL OF CHEMISTRY · 2017 ·Vol. 41 ·期 9 ·3273-3279 · IF 3.269

Low generation PAMAM-based nanomicelles as ROS-responsive gene vectors with enhanced transfection efficacy and reduced cytotoxicity in vitro

Chen-Tao Xu,Guang Chen,Xuan Nie,Long-Hai Wang,Sheng-Gang Ding,Ye-Zi You

Poly(amidoamine)s (PAMAMs) of high-generations (G > 5) exhibit high efficacy in gene transfection, but their high cost and severe cytotoxicity limit their use in biomedicine. In contrast, PAMAMs of low-generations (G < 3) are less toxic and easy to synthesize, but exhibit low transfection efficacy. In this report, we design a novel amphiphilic dendrimer by conjugating reactive oxygen species (ROS)-responsive poly(propylenesulfide) (PPS) to a low generation PAMAM dendrimer (G = 2, Mw = 3500 Da) via disulfide bonds. This amphiphilic conjugate can self-assemble into stable nanomicelles. The results show that the obtained nanomicelles have a high zeta potential, which can condense DNA tightly. Moreover, the DNA/nanomicelle polyplexes can be fully dissociated by intracellular ROS and easily release the entrapped DNA. As gene vectors, the nanomicelles exhibited high transfection efficacy and fairly low cytotoxicity in vitro.

研究领域: 生物材料学 · 分子生物学 · 药剂学
✓ 已验证 DOI 高影响因子
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JOURNAL OF CHEMOMETRICS · 2025 ·Vol. 39 ·期 3 ·e70013 · IF 2.1

Novel Sexalinear Decomposition Algorithm for Analyzing the Chemical Sexalinear Data Array

Yue-Yue Chang,Qiu-Na Shi,Tong Wang,Hai-Long Wu,Ru-Qin Yu

With the development of analytical instrument towards more and more high-way and complex, it is very important and meaningful work to obtain ultra-high-way chemical data and explore its analytical methods. In this paper, a novel and excellent six-way algorithm combination method (six-way ACM) was proposed. In addition, a real chemically meaningful ultra-high-way sexalinear data array was obtained and constructed for the first time. The proposed six-way data array has highly collinearity, which puts forward higher requirements for parsing this data array to a certain extent. To verify the feasibility of the proposed algorithm, it was used to analyze the above real sexalinear six-way data array and a series of simulated six-way data arrays with different noise levels. The results of real data and simulated data demonstrate that the proposed method can be well used in the analysis of six-way data arrays and shows fascinating performance, including insensitive to excessive number of components, fast convergence speed, and suitable for high collinearity and high noise data. Compared with three-way, four-way, and five-way calibration methods, the six-way ACM provides higher sensitivity, a lower limit of detection, a lower limit of quantification, and more stable and accurate results, showing an outstanding “higher-order advantages” and better ability to handle collinearity problems. This work provides not only data analysis method for high-order instruments that may emerge in the future but also real data support and methodological reference for theoretical research on high-order tensor algebra.

CAS / MDL: 23103-98-2 107534-96-3
研究领域: 分析化学 · 计算化学 · 数据科学
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JOURNAL OF POLYMER SCIENCE PART A-POLYMER CHEMISTRY · 2018 ·Vol. 56 ·期 13 ·1446-1456 · IF 2.588

Self-assembly behavior of amphiphilic linear-block-dendritic copolymers with long subchains: Dependences on dendron generation and mixing dynamics

Peng-Yun Li,Chen He,Wei-Xiang Xie,Hui-Juan Li,Abdul Haleem,Chuan-Shan Hu,Xi-Chuan Li,Wei-Dong He

Block copolymers composed of acrylic acid and methyl methacrylate with three topologies of double linear blocks, poly(acrylic acid) (PAA) linear block/poly(methyl methacrylate) (PMMA) G1-dendron and PAA linear block/PMMA G2-dendron have been prepared by the combination of atom transfer radical polymerization and azide–alkyne click reaction. Proton nuclear magnetic resonance spectroscopy, Fourier transform infrared spectroscopy, and gel permeation chromatography have been adopted thoroughly to identify the chemical structure of those block copolymers with expected topologies. The self-assembly of those block copolymers in the selective solvent has been performed through two mixing routes of gentle and abrupt variation in solvent selectivity, and the morphology of the obtained self-assemblies/aggregates was observed by transmission electron microscopy. Because the abrupt variation route altered sharply the solvent quality during the mixing, the intermolecular association of polymer chains resulted in the smaller self-assemblies but the further growth of smaller self-assemblies was not observed. On the contrary, the gentle variation route changed gradually the solvent quality during the mixing, favoring not only the intermolecular association but also the further growth of self-assemblies to result in larger aggregates. The final morphology of those assemblies/aggregates also exhibited the dependence of PMMA dendron generation. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018 , 56 , 1446–1456

研究领域: 高分子化学 · 材料科学
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RSC Advances · 2015 ·Vol. 5 ·期 44 ·35282-35290 · IF 3.84

The key effect of the self-assembly mechanism of dendritic gelators: solubility parameters, generations and terminal effects

Si Chen,Guodong Tang,Bozhen Wu,Meng Ma,Xu Wang

The key effect of the self-assembly mechanism of dendritic gelators is researched by a comprehensive investigation of the gelation behavior of L-lysine dendritic gelators with different structures of three generations in 20 different solvents. The solvents investigation, 1H NMR, tube inversion method, DSC, rheology, FTIR and rheological measurements show that the reported dendritic gelators self-assemble through the main driving force of hydrogen bonds and the second driving force of π–π stackings. So the key effect of the self-assembling mechanism is that these factors can influence the driving force of the self-assembly process. This is the reason that L-lysine dendritic gelators tend to gelate in solvents with low α and β parameter values, which have less influence on the formation of hydrogen bonds between the gelators. Higher generations provide a much greater hydrogen bond density in the gelators, which makes them have a higher gelation ability. The benzyl terminal groups provide the second driving force of π–π stacking, making the Bzl-Gly-Lys gelators have much stronger gelation ability. This research reports a comprehensive insight into the precise ways in which the solubility parameters of the solvents, the gelator generation and the terminal group effects can influence the self-assembly and gelation of dendritic gelators. Gaining this type of fundamental understanding is essential if the key effect of this important class of self-assembling soft materials is to be truly understood.

研究领域: 材料科学 · 化学 · 纳米技术 · 物理化学
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JOURNAL OF PROTEOME RESEARCH · 2014 · IF 5.001

Simultaneous Quantification of Protein Phosphorylation Sites using Liquid Chromatography–Tandem Mass Spectrometry-Based Targeted Proteomics: A Linear Algebra Approach for Isobaric Phosphopeptides

Feifei Xu,Ting Yang,Yuan Sheng,Ting Zhong,Mi Yang,Yun Chen

As one of the most studied post-translational modifications (PTM), protein phosphorylation plays an essential role in almost all cellular processes. Current methods are able to predict and determine thousands of phosphorylation sites, whereas stoichiometric quantification of these sites is still challenging. Liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS)-based targeted proteomics is emerging as a promising technique for site-specific quantification of protein phosphorylation using proteolytic peptides as surrogates of proteins. However, several issues may limit its application, one of which relates to the phosphopeptides with different phosphorylation sites and the same mass (i.e., isobaric phosphopeptides). While employment of site-specific product ions allows for these isobaric phosphopeptides to be distinguished and quantified, site-specific product ions are often absent or weak in tandem mass spectra. In this study, linear algebra algorithms were employed as an add-on to targeted proteomics to retrieve information on individual phosphopeptides from their common spectra. To achieve this simultaneous quantification, a LC–MS/MS-based targeted proteomics assay was first developed and validated for each phosphopeptide. Given the slope and intercept of calibration curves of phosphopeptides in each transition, linear algebraic equations were developed. Using a series of mock mixtures prepared with varying concentrations of each phosphopeptide, the reliability of the approach to quantify isobaric phosphopeptides containing multiple phosphorylation sites (≥2) was discussed. Finally, we applied this approach to determine the phosphorylation stoichiometry of heat shock protein 27 (HSP27) at Ser78 and Ser82 in breast cancer cells and tissue samples.

CAS / MDL: 64-18-6 76-05-1
研究领域: 蛋白质组学 · 生物化学 · 质谱分析 · 癌症生物学
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ACS Biomaterials Science & Engineering · 2022 · IF 5.395

Cationic Amphiphilic Dendrons with Anticancer Activity

Wei Guo,Wenchang Liu,Pengqi Wan,Hao Wang,Chunsheng Xiao,Li Chen,Xuesi Chen

Cancer has become the leading cause of human death worldwide, and there is an urgent need to design and develop new oncology drugs. In this study, we report series of cationic amphiphilic dendrons with different hydrophobic alkyl chains (Cn) and different generations (Gx) and demonstrate their use for anticancer applications. The results revealed that lower-generation dendrons (G1) with a longer hydrophobic alkyl chain (C12 and C18) have stronger antitumor activity. Among these dendrons, a lead candidate C12–G1 was identified that demonstrated excellent broad-spectrum antitumor activity in 7 cancer cell lines including highly metastatic tumor cells, while simultaneously, hemolysis was negligible. Mechanistic studies showed that C12–G1 could lead to cytoplasmic leakage and induce cancer cell necrosis through membrane disruption. In addition, C12–G1 showed potent inhibition of tumor growth in a B16–F10 melanoma model. In conclusion, these findings demonstrate that the cationic amphiphilic dendron might be a promising agent for anticancer application.

CAS / MDL: 24424-99-5 96-33-3
研究领域: 药学 · 肿瘤学 · 分子生物学
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