Novel Cationic Polymers Designed for Non-Viral Gene Delivery

Zhiyuan Zhong,Chao Lin,Yan Song,Martin C. Lok,Xulin Jiang,Lane V. Christensen,Johan F.J. Engbersen,Sung Wan Kim,Wim E. Hennink,Jan Feijen 한국고분자학회 2006 한국고분자학회 학술대회 연구논문 초록집 Vol.2006 No.10

Design of Multifunctional Degradable Polymeric Nanosystems for Active Tumor-Targeting Drug Delivery

Yinan Zhong,Ru Cheng,Chao Deng,Fenghua Meng,Jian Zhang,Zhiyuan Zhong 한국고분자학회 2014 한국고분자학회 학술대회 연구논문 초록집 Vol.2014 No.10

Flexural Capacity Prediction Model For Steel Fibre‑Reinforced Concrete Beams

Aocheng Zhong,Massoud Sofi,Elisa Lumantarna,Zhiyuan Zhou,Priyan Mendis 한국콘크리트학회 2021 International Journal of Concrete Structures and M Vol.15 No.4

Steel fibre (SF) reinforcement has been shown to improve the ductility of high strength concrete (HSC), which is known to be brittle. Research conducted to date on steel fibre reinforced concrete and its effects have emphasised post-failure performance and cracking mechanism. The difficulty in predicting the behaviour of fibres is due to the randomly distributed nature of the material within the matrix leading to a probability distribution of results. Published literature has shown a benefit of adding steel fibres in terms of the ductility performance of structures. Clearly, there is a potential for such material as replacement of conventional steel reinforcement. This study proposes a theoretical model of evaluating the potential of using steel fibres as a replacement material to conventional steel reinforcement bars based on the case study, laboratory and theoretical methodologies. The compressive strength of the concrete at key dates, the effective fibre cross-sectional were measured, and a prediction model was created based on the measurement parameters. The use of four-point flexural testing, standard compressive testing and software image modelling provided the study with relevant data used to analyse and compare to the prediction. Greater ductility performance and toughness were observed with increased fibre volumes, confirming proposed predictions and conclusion drawn from published literature. No consistent or conclusive correlations between fibre volumes and the compressive strength of concrete were found. A relationship between fibre volumes and predicted moment capacities of steel fibre reinforced concrete beams was found based on the proposed theoretical flexural analysis method.

pH-Sensitive Degradable Hydrophobe Modified 1.8 kDa Branched Polyethylenimine as “Artificial Viruses” for Safe and Efficient Intracellular Gene Transfection

Meng Zheng,Zhiyuan Zhong,Chunmei Yang,Fenghua Meng,Rui Peng 한국고분자학회 2012 Macromolecular Research Vol.20 No.3

1.8 kDa branched polyethylenimine (PEI) was modified with pH-sensitive degradable acetal containing hydrophobe, 2,4,6-trimethoxybenzylidene-tris(hydroxymethyl)ethane (TMB-THME), to enhance its DNA condensation under extracellular conditions as well as to achieve active DNA release inside cells. PEI-(TMBTHME)n conjugates in the amount of 1.8 kDa were prepared with varying degrees of substitution (DS) from 3.0, 5.7 to 10.1. Notably, dynamic light scattering (DLS) measurements showed that all three 1.8 kDa PEI-(TMB-THME)n conjugates could effectively condense DNA into nano-sized particles (189-197 nm) at N/P ratios ranging from 20/1 to 80/1. The surface charges of PEI-(TMB-THME)n polyplexes depending on DS and N/P ratios varied from +22 to +28 mV,which were comparable to or slightly higher than the unmodified 1.8 kDa PEI counterparts (~+22 to +23 mV). Under a mildly acidic condition mimicking that of endosomes, interestingly, 1.8 kDa PEI-(TMB-THME)n polyplexes were quickly unpacked to release DNA because of the pH-induced acetal degradation that transforms hydrophobic modification into hydrophilic modification. MTT assays demonstrated that all PEI-(TMB-THME)n polyplexes displayed low cytotoxicity (>80%) to 293T, and HeLa cells at N/P ratios ranging from 20/1 to 60/1. The in vitro gene transfection studies showed that the transfection activity of 1.8 kDa PEI was significantly enhanced by modifications with TMBTHME,in which transfection efficiencies increased with increasing DS. For example, 1.8 kDa PEI-(TMBTHME)10.1 polyplexes displayed 250-fold and 80-fold higher transfection efficiencies than those of the unmodified 1.8 kDa PEI counterparts in 293T and HeLa cells, respectively, which were approximately 4-fold and 2-fold higher than that of 25 kDa PEI control. The superior transfection activity of 1.8 kDa PEI-(TMB-THME)10.1 polyplexes was also confirmed by confocal laser scanning microscopy (CLSM), which showed efficient delivery of DNA into the nuclei of 293T cells following 4 h transfection. Modification of low molecular weight PEI with pH-sensitive degradable hydrophobe has appeared to be highly promising in the development of “artificial viruses” for safe and efficient gene transfer.

Copper Can Still Be Epitaxially Deposited on Palladium Nanocrystals To Generate Core–Shell Nanocubes Despite Their Large Lattice Mismatch

Jin, Mingshang,Zhang, Hui,Wang, Jinguo,Zhong, Xiaolan,Lu, Ning,Li, Zhiyuan,Xie, Zhaoxiong,Kim, Moon J.,Xia, Younan American Chemical Society 2012 ACS NANO Vol.6 No.3

<P>Here we report the synthesis of Pd@Cu core–shell nanocubes <I>via</I> epitaxial growth, where the lattice mismatch is 7.1%. The synthesis involved the use of Pd seeds with different shapes (including cubes, cuboctahedra, and octahedra) for the epitaxial growth of Cu shells. Different from the conventional growth mode, Cu atoms initially nucleated only on a few of the many faces of a Pd seed, onto which more Cu atoms were continuously added to generate Cu blocks. Later, the Cu atoms also started to nucleate and grow on other faces of the Pd seed until the entire surface of the seed was covered by a Cu shell. As a result, the Pd seed was rarely located in the center of each core–shell structure. The final product took a cubic shape enclosed by {100} facets regardless of the type of Pd seeds used because of the selective capping of Cu(100) surface by hexadecylamine. The edge lengths of the Pd@Cu nanocubes could be tuned from 50 to 100 nm by varying the amount of Pd seeds while keeping the amount of CuCl<SUB>2</SUB> precursor.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/ancac3/2012/ancac3.2012.6.issue-3/nn2050278/production/images/medium/nn-2011-050278_0001.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/nn2050278'>ACS Electronic Supporting Info</A></P>

Biological Characteristics of Recombinant Arthrobotrys oligospora Chitinase AO-801

Gong, Shasha,Meng, Qingling,Qiao, Jun,Huang, Yunfu,Zhong, Wenqiang,Zhang, Guowu,Zhang, Kai,Li, Ningxing,Shang, Yunxia,Li, Zhiyuan,Cai, Xuepeng The Korea Society for Parasitology and Tropical Me 2022 The Korean Journal of Parasitology Vol.60 No.5

Chitinase AO-801 is a hydrolase secreted by Arthrobotrys oligospora during nematode feeding, while its role remained elusive. This study analyzed the molecular characteristics of recombinant chitinase of Arthrobotrys oligospora (reAO-801). AO-801 belongs to the typical glycoside hydrolase 18 family with conserved chitinase sequence and tertiary structure of (α/β)₈ triose-phosphate isomerase (TIM) barrel. The molecular weight of reAO-801 was 42 kDa. reAO-801 effectively degraded colloidal and powdered chitin, egg lysate, and stage I larval lysate of Caenorhabditis elegans. The activity of reAO-801 reached its peak at 40℃ and pH values between 4-7. Enzyme activity was inhibited by Zn2⁺, Ca2⁺, and Fe3⁺, whereas Mg2⁺ and K⁺ potentiated its activity. In addition, urea, sodium dodecyl sulfate, and 2-mercaptoethanol significantly inhibited enzyme activity. reAO-801 showed complete nematicidal activity against C. elegans stage I larvae. reAO-801 broke down the C. elegans egg shells, causing them to die or die prematurely by hatching the eggs. It also invoked degradation of Haemonchus contortus eggs, resulting in apparent changes in the morphological structure. This study demonstrated the cytotoxic effect of reAO-801, which laid the foundation for further dissecting the mechanism of nematode infestation by A. oligospora.

Dual bio-responsive gene delivery via reducible poly(amido amine) and survivin-inducible plasmid DNA

Namgung, Ran,Brumbach, Jonathan H.,Jeong, Ji Hoon,Yockman, James W.,Kim, Sung Wan,Lin, Chao,Zhong, Zhiyuan,Feijen, Jan,Engbersen, Johan F. J.,Kim, Won Jong Springer-Verlag 2010 Biotechnology letters Vol.32 No.6

<P>A bioreducible poly(amido amine) (SS-PAA) gene carrier, known as poly (amido-butanol) (pABOL), was used to transfect a variety of cancer and non-cancer cell lines. To obtain cancer-specific transgene expression for therapeutic efficiency in cancer treatment, we constructed survivin-inducible plasmid DNA expressing the soluble VEGF receptor, sFlt-1, downstream of the survivin promoter (pSUR-sFlt-1). Cancer-specific expression of sFlt-1 was observed in the mouse renal carcinoma (RENCA) cell line. pABOL enhanced the efficiency of gene delivery compared to traditional carriers used in the past. Thus, a dual bio-responsive gene delivery system was developed by using bioreducible p(ABOL) for enhanced intracellular gene delivery and survivin-inducible gene expression system (pSUR-sFlt-1 or pSUR-Luc reporter gene) that demonstrates increased gene expression in cancer that has advantages over current gene delivery systems.</P>

Cationic methacrylate copolymers containing primary and tertiary amino side groups: Controlled synthesis via RAFT polymerization, DNA condensation, and in vitro gene transfection

Zhu, Caihong,Jung, Sooyeon,Si, Guoying,Cheng, Ru,Meng, Fenghua,Zhu, Xiulin,Park, Tae Gwan,Zhong, Zhiyuan Wiley Subscription Services, Inc., A Wiley Company 2010 Journal of polymer science Part A, Polymer chemist Vol.48 No.13

<P>A versatile family of cationic methacrylate copolymers containing varying amounts of primary and tertiary amino side groups were synthesized and investigated for in vitro gene transfection. Two different types of methacrylate copolymers, poly(2-(dimethylamino)ethyl methacrylate)/aminoethyl methacrylate [P(DMAEMA/AEMA)] and poly(2-(dimethylamino)ethyl methacrylate)/aminohexyl methacrylate [P(DMAEMA/AHMA)], were obtained by reversible addition-fragmentation chain transfer (RAFT) copolymerization of dimethylaminoethyl methacrylate (DMAEMA) with N-(tert-butoxycarbonyl)aminoethyl methacrylate (Boc-AEMA) or N-(tert-butoxycarbonyl)aminohexyl methacrylate (Boc-AHMA) followed by acid deprotection. Gel permeation chromatography (GPC) measurements revealed that Boc-protected methacrylate copolymers had M<SUB>n</SUB> in the range of 16.1–23.0 kDa and low polydispersities of 1.12–1.26. The copolymer compositions were well controlled by monomer feed ratios. Dynamic light scattering and agarose gel electrophoresis measurements demonstrated that these PDMAEMA copolymers had better DNA condensation than PDMAEMA homopolymer. The polyplexes of these copolymers revealed low cytotoxicity at an N/P ratio of 3/1. The in vitro transfection in COS-7 cells in serum free medium demonstrated significantly enhanced (up to 24-fold) transfection efficiencies of PDMAEMA copolymer polyplexes as compared with PDMAEMA control. In the presence of 10% serum, P(DMAEMA/AEMA) and P(DMAEMA/AHMA) displayed a high transfection activity comparable with or better than 25 kDa PEI. These results suggest that cationic methacrylate copolymers are highly promising for development of safe and efficient nonviral gene transfer agents. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 2869–2877, 2010</P> <B>Graphic Abstract</B> <P>A versatile family of cationic PDMAEMA copolymers containing varying amounts of primary and tertiary amine groups were designed and synthesized by controlled RAFT copolymerization. These novel copolymers showed improved DNA condensation and dramatically enhanced gene transfection as compared with the PDMAEMA homopolymer. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.] <img src='wiley_img_2010/0887624X-2010-48-13-POLA24064-gra001.gif' alt='wiley_img_2010/0887624X-2010-48-13-POLA24064-gra001'> </P>