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polymer and gene

Peng Liu, Shengfeng Wang, Xuanjun Liu, Jinsong Ding, Wenhu Zhou
Cisplatin (CisPt) is one of the most effective antitumor drugs against a wide range of solid cancers, and recent studies have indicated that combination of CisPt and RNA interference (RNAi) agents would effectively enhance therapeutic index, while the development of simple yet robust dual-delivery systems still remains a challenge. Here, we demonstrated that platinated graphene oxide is an excellent platform to achieve such goal. Nano-Graphene oxide (NGO) was easily platinated by CisPt, and the resulting CisPt/NGO was characterized by several aspects...
June 12, 2018: European Journal of Pharmaceutical Sciences
Tamunonengiyeofori Lawson, Sean Mayes, Grantley W Lycett, Chiew Foan Chin
Fruit ripening is a complex developmental process that involves the synthesis and modification of the cell wall leading up to the formation of an edible fruit. During the period of fruit ripening, new cell wall polymers and enzymes are synthesized and trafficked to the apoplast. Vesicle trafficking has been shown to play a key role in facilitating the synthesis and modification of cell walls in fruits. Through reverse genetics and gene expression studies, the importance of Rab guanosine triphosphatases (GTPases) as integral regulators of vesicle trafficking to the cell wall has been revealed...
June 14, 2018: Biotechnology & Genetic Engineering Reviews
Xiao-Jiao Du, Ze-Yu Wang, Yu-Cai Wang
The development of delivery systems for small interfering RNA (siRNA) plays a key role in its clinical application. As the major delivery systems for siRNA, cationic polymer- or lipid-based vehicles are plagued by inherent issues. As proof of concept, a disulfide bond-containing amphiphilic Janus dendrimer (ssJD), which could be conveniently synthesized and readily scaled up with high reproducibility, was explored as a siRNA delivery system to circumvent these issues. The cationic hydrophilic head of this Janus dendrimer ensured strong and stable binding with negatively charged siRNA via electrostatic interactions, and the loaded siRNA was rapidly released from the obtained complexes under a redox environment...
June 14, 2018: Biomaterials Science
Jia Liu, Xingxin Liu, Ye Yuan, Qilin Li, Bingcheng Chang, Luming Xu, Bo Cai, Chao Qi, Cao Li, Xulin Jiang, Guobin Wang, Zheng Wang, Lin Wang
Since heterogeneity affects many functional aspects of a tumor, a way to overcome it is to arm nanosized drug delivery systems (nanoDDS) with diverse functions required to shatter heterogeneity. However, it remains technically challenging to fabricate a nanocarrier possessing all required functions. Here we propose a modular strategy for generating a supramolecular, multifunctional, stimuli-responsive nanoDDS through docking a parental core nanoDDS with various daughter function-prebuilt modules. Doxorubicin loaded mesoporous silica nanoparticles (MSNs) as the parental nano-core are wrapped by poly(β-cyclodextrin) (PCD) as a gatekeeper through host-guest interactions between cyclodextrin and pyridine groups of pyridine-disulfide bonds that confers pH/redox dual responsiveness, thus constructing stimuli-responsive nanoDDS (DOX@PRMSNs)...
June 12, 2018: ACS Applied Materials & Interfaces
Denise Tornavoi de Castro, Cássio do Nascimento, Oswaldo Luiz Alves, Emerson de Souza Santos, José Augusto Marcondes Agnelli, Andréa Cândido Dos Reis
OBJECTIVES: This study characterized the microbial diversity of formed biofilm on the surface of acrylic resins modified with nanostructured silver vanadate decorated with silver nanoparticles (AgVO3 ) after incubation in human saliva. DESIGN: Resin specimens prepared with AgVO3 at concentrations 0%, 1%, 2.5%, and 5% by either vacuum mixing or polymer solubilization were characterized by scanning electron microscopy (SEM) and X-ray diffraction (XRD). After 24 h and 7 days of saliva incubation, biofilm samples were collected from the surface of the specimens...
June 5, 2018: Archives of Oral Biology
Yuri Takeda, Yuki Tobimatsu, Steven D Karlen, Taichi Koshiba, Shiro Suzuki, Masaomi Yamamura, Shinya Murakami, Mai Mukai, Takefumi Hattori, Keishi Osakabe, John Ralph, Masahiro Sakamoto, Toshiaki Umezawa
p-Coumaroyl ester 3-hydroxylase (C3'H) is a key enzyme involved in the biosynthesis of lignin, a phenylpropanoid polymer that is the major constituent in vascular plants' secondary cell walls. Although the crucial role of C3'H in lignification and its manipulation to upgrade lignocellulose have been investigated in eudicots, limited information is available in monocotyledonous grass species despite their potential as biomass feedstocks. Here we address the pronounced impacts of C3'H-deficiency on the structure and properties of grass cell walls...
June 11, 2018: Plant Journal: for Cell and Molecular Biology
Sungjin Min, Yoonhee Jin, Chen Yuan Hou, Jayoung Kim, Jordan J Green, Taek Jin Kang, Seung-Woo Cho
Here, a novel anticancer gene therapy with a bacterial tRNase gene, colicin D or virulence associated protein C (VapC), is suggested using biodegradable polymeric nanoparticles, such as poly(β-amino esters) (PBAEs) as carriers. These genes are meticulously selected, aiming at inhibiting translation in the recipients by hydrolyzing specific tRNA species. In terms of nanoparticles, out of 9 PBAE formulations, a leading polymer, (polyethylene oxide)4 -bis-amine end-capped poly(1,4-butanediol diacrylate-co-5-amino-1-pentanol) (B4S5E5), is identified that displays higher gene delivery efficacy to cancer cells compared with the leading commercial reagent Lipofectamine 2000...
June 10, 2018: Advanced Healthcare Materials
Ludger Johannes, Marco Lucchino
RNA interference (RNAi) is a fundamental cellular process for the posttranscriptional regulation of gene expression. RNAi can exogenously be modulated by small RNA oligonucleotides, such as microRNAs (miRNAs) and small interfering RNAs (siRNAs), or by antisense oligonucleotides. These small oligonucleotides provided the scientific community with powerful and versatile tools to turn off the expression of genes of interest, and hold out the promise of new therapeutic solutions against a wide range of gene-associated pathologies...
June 2018: Nucleic Acid Therapeutics
Edoardo Giacopuzzi, Mattia Laffranchi, Romina Berardelli, Viola Ravasio, Ilaria Ferrarotti, Bibek Gooptu, Giuseppe Borsani, Annamaria Fra
The growth of publicly available data informing upon genetic variations, mechanisms of disease and disease sub-phenotypes offers great potential for personalised medicine. Computational approaches are likely required to assess large numbers of novel genetic variants. However, the integration of genetic, structural and pathophysiological data still represents a challenge for computational predictions and their clinical use. We addressed these issues for alpha-1-antitrypsin deficiency, a disease mediated by mutations in the SERPINA1 gene encoding alpha-1-antitrypsin...
June 7, 2018: Human Mutation
Yuhang Jiang, Alice Gaudin, Junwei Zhang, Tushar Agarwal, Eric Song, Amy C Kauffman, Gregory T Tietjen, Yongheng Wang, Zhaozhong Jiang, Christopher J Cheng, W Mark Saltzman
Gene delivery is known to be a complicated multi-step biological process. It has been observed that subtle differences in the structure and properties of polymeric materials used for gene delivery can lead to dramatic differences in transfection efficiency. Therefore, screening of properties is pivotal to optimizing the polymer. So far, most polymeric materials are built in a "bottom-up" manner, i.e. synthesized from monomers that allow modification of polymer composition or structural factors. With this method, we previously synthesized and screened a library of biodegradable poly(amine-co-ester) (PACE) terpolymers for optimized DNA delivery...
May 25, 2018: Biomaterials
Charis-Patricia Segeritz, Sheikh Tamir Rashid, Miguel Cardoso de Brito, Maria Serra Paola, Adriana Ordonez, Carola Maria Morell, Joseph E Kaserman, Pedro Madrigal, Nicholas Hannan, Laurent Gatto, Lu Tan, Andrew A Wilson, Kathryn Lilley, Stefan J Marciniak, Bibekbrata Gooptu, David A Lomas, Ludovic Vallier
BACKGROUND AND AIMS: α1 -antitrypsin deficiency (A1ATD) is an autosomal recessive disorder caused by mutations in the SERPINA1 gene. Individuals with the Z variant (Gly342Lys) retain polymerised protein in the endoplasmic reticulum (ER) of their hepatocytes, predisposing them to liver disease. The concomitant lack of circulating A1AT also causes lung emphysema. Greater insight into the mechanisms that link protein misfolding to liver injury will facilitate the design of novel therapies...
June 4, 2018: Journal of Hepatology
Lili Du, Changrong Wang, Lingwei Meng, Qiang Cheng, Junhui Zhou, Xiaoxia Wang, Deyao Zhao, Jianhua Zhang, Liandong Deng, Zicai Liang, Anjie Dong, Huiqing Cao
Tri-block copolymers have exhibited great potentials in small interfering RNA (siRNA) therapeutics. To reveal structure-activity relationships, we here synthesized a series of tri-block copolymers with different hydrophobic segments, PEG-PAMA-P(C6Ax -C7Ay -DPAz -DBAm ) (EAAS) and PEG-PDAMAEMA-P(C6Ax -C7Ay -DPAz -DBAm ) (EDAS), termed from EAASa to EAASh and EDASa to EDASh, with pKa ranging from 5.2 to 7.0. Our data showed that the better gene silencing efficiency was located in pKa of 5.8-6.2, which was contributed from higher endosomal escape observed with confocal images and hemolysis assay...
May 29, 2018: Biomaterials
Zheng Luo, Yang Xu, Enyi Ye, Zibiao Li, Yun-Long Wu
Gold nanoparticles (AuNPs), with elegant thermal, optical, or chemical properties due to quantum size effects, may serve as unique species for therapeutic or diagnostic applications. It is worth mentioning that their small size also results in high surface activity, leading to significantly impaired stability, which greatly hinders their biomedical utilizations. To overcome this problem, various types of macromolecular materials are utilized to anchor AuNPs so as to achieve advanced synergistic effect by dispersing, protecting, and stabilizing the AuNPs in polymeric-Au hybrid self-assemblies...
June 4, 2018: Macromolecular Rapid Communications
Forouhe Zahir-Jouzdani, Masoud Soleimani, Mirgholamreza Mahbod, Fatemeh Mottaghitalab, Faezeh Vakhshite, Ehsan Arefian, Saeed Shahhoseini, Rasoul Dinarvand, Fatemeh Atyabi
Chemical burns are major causes of corneal blindness. Transforming growth factor beta-1 (TGFβ1 ) plays an important role in induction of corneal inflammation-related-fibrosis leading to the blindness. Here, a topical delivery system consisting anti-fibrotic TGF-β1 siRNA, an inflammatory suppressing gene, was designed for treatment of corneal injuries. TGF-β1 siRNA loaded in nanoparticles (NPs) made up of polyethyleneimine polymer demonstrated high fibroblast transfection efficiency. Moreover, TGF-β 1 and PDGF genes and ECM deposition were suppressed in isolated human corneal fibroblasts...
June 4, 2018: Drug Delivery and Translational Research
James K Deyling, Edward M Turk, Nolan B Holland
Elastin-like polypeptides (ELPs) are stimuli-responsive polymers consisting of peptide repeat units from the elastin protein. Most commonly these materials are biosynthesized in E. coli using genes that have been built by standard molecular biology techniques. The inherent repetitive nature of these polypeptides makes the construction of genes that encode them more challenging than for typical recombinant proteins. Described here is a robust technique to produce genes encoding long chains of ELP through successive rounds of Gibson assembly that nearly double the ELP length with each cloning iteration...
2018: Methods in Molecular Biology
Sheng-Xue Xie, Abdulgader Baoum, Nabil A Alhakamy, Cory J Berkland
Four molecular weights of poly-L-lysine (PLL) [1,000-5,000 Da, 1,500-8,000 Da, 4,000-15,000 Da and 15,000-30,000 Da] and three molecular weights of polyethyleneimine (PEI) [800 Da, 2,000 Da, and 25,000 Da] were used to systematically study the effect of calcium (Ca2+ ) to improve transfection efficiency of polyelectrolyte complexes. Complexes made using different molecular weights of PLL or PEI polymer showed clear differences in the levels of gene expression in the presence and absence of calcium chloride when tested using A549 human lung carcinoma cells...
June 1, 2018: International Journal of Pharmaceutics
Kyoungnam Kim, Kitae Ryu, Yeon Su Choi, Yong-Yeon Cho, Joo Young Lee, Hye Suk Lee, Han Chang Kang
Though α-poly(L-lysine) (APL) has been well-studied in gene delivery, ε-poly(L-lysine) (EPL) with same repeating unit of L-lysine but different structure has been rarely investigated. This study compared various effects of their different structures in gene delivery processes. EPL showed less cytotoxicity and more proton buffering capacity for endosomal release than APL. Also, EPL/pDNA polyplexes represented higher nucleus preference than APL/pDNA polyplexes. However, EPL had weaker affinities with pDNA than APL, leading to formation of larger EPL/pDNA complexes with less compactness and successively faster decomplexation...
June 4, 2018: Biomacromolecules
Lotte M P Vermeulen, Stefaan C De Smedt, Katrien Remaut, Kevin Braeckmans
In non-viral gene therapy, cationic polymers and lipids are frequently used to encapsulate macromolecular therapeutics into nanoparticles. During their journey to deliver the cargo to the intended intracellular target, many biological barriers need to be overcome. One of the major bottlenecks for efficient transfection is the endosomal barrier since nanoparticles often remain entrapped inside endosomes and are trafficked towards the lysosomes where the cargo is degraded. For cationic polymers, the proton sponge hypothesis was introduced in the late '90s as a way to explain their endosomal escape properties...
May 30, 2018: European Journal of Pharmaceutics and Biopharmaceutics
Yi-Fan Li, Hou-Ting Zhang, Lin Xin
BACKGROUND: Gastric cancer (GC) is the second most common leading cause of cancer-related death. Cancer stem cell (CSC) with the mark of CD44 played an important role in GC. rMETase was wildly exploited as chemotherapeutic option for GC. Polymers synthetic nanoparticle drug delivery systems have been commonly used for cancer therapy. With the decorating of Hyaluronic acid (HA), a receptor of CD44, nanoparticles exhibit with good biocompatibility and aqueous solubility. METHODS: The characteristic of nanoparticles (NPs) was analyzed by TEM and DLS...
June 1, 2018: Journal of Cancer Research and Clinical Oncology
Matthew R Tucker, Haoyu Lou, Matthew K Aubert, Laura G Wilkinson, Alan Little, Kelly Houston, Sara C Pinto, Neil J Shirley
The majority of organs in plants are not established until after germination, when pluripotent stem cells in the growing apices give rise to daughter cells that proliferate and subsequently differentiate into new tissues and organ primordia. This remarkable capacity is not only restricted to the meristem, since maturing cells in many organs can also rapidly alter their identity depending on the cues they receive. One general feature of plant cell differentiation is a change in cell wall composition at the cell surface...
May 31, 2018: Plants (Basel, Switzerland)
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