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polymers and gene transfer

Xiao-Yan Tu, Chao Meng, Xiao-Long Zhang, Miao-Ge Jin, Xian-Shuo Zhang, Xue-Zhi Zhao, Yun-Fei Wang, Li-Wei Ma, Bao-Yan Wang, Ming-Zhu Liu, Hua Wei
The cyclic brush polymers, due to the unique topological structure, have shown in the previous studies higher delivery efficacy than the bottlebrush analogues as carriers for drug and gene transfer. However, to the best of knowledge, the preparation of reduction-sensitive cyclic brush polymers for drug delivery applications remains unexplored. For this purpose, a reduction-sensitive amphiphilic cyclic brush copolymer, poly(2-hydroxyethyl methacrylate-g-poly(ε-caprolactone)-disulfide link-poly(oligoethyleneglycol methacrylate)) (P(HEMA-g-PCL-SS-POEGMA)) with reducible block junctions bridging the hydrophobic PCL middle layer and the hydrophilic POEGMA outer corona is designed and synthesized successfully in this study via a "grafting from" approach using sequential ring-opening polymerization (ROP) and atom transfer free radical polymerization (ATRP) from a cyclic multimacroinitiator PHEMA...
May 10, 2018: Macromolecular Bioscience
Wenyi Zhong, Li Jiang, Xu Wang, Aimin Huang, Lishuo Li, Lin Ma
Polyethyleneimine (PEI) has long been considered as "golden standard" for polymeric gene delivery carriers. To get a better understanding on the molecular basis of PEI cytotoxicity, dynamic light scattering, zeta-potential measurement, fluorescence emission, Fröster resonance energy transfer and anisotropy measurement were conducted to reveal the interaction between PEI and dimyristoylphosphatidylcholine (DMPC) liposome and the influence on the structural properties of the membrane. PEI was found to bind onto the surface of the liposome, inducing an aggregation of the vesicle and an increase in surface potential at low PEI concentration up to 0...
April 27, 2018: Colloids and Surfaces. B, Biointerfaces
Ulrich S Schubert, Tanja Bus, Martin Reifarth, Johannes C Brendel, Stephanie Hoeppener, Anja Traeger, Anne-Kristin Trützschler
Methacrylate-based polymers represent promising non-viral gene delivery vectors, since they offer a large variety of polymer architectures and functionalities, which are beneficial for specific demands in gene delivery. In combination with controlled radical polymerization techniques, such as the reversible addition-fragmentation chain transfer polymerization, the synthesis of well-defined polymers is possible. In this study we prepared a library of defined linear polymers based on (2-aminoethyl)-methacrylate (AEMA), N-methyl-(2-aminoethyl)-methacrylate (MAEMA) and N,N-dimethyl-(2-aminoethyl)-methacrylate (DMAEMA) monomers, bearing pendant primary, secondary and tertiary amino groups, and investigated the influence of the substitution pattern on their gene delivery ability...
May 1, 2018: Bioconjugate Chemistry
Haobin Chen, Xiaofeng Fang, Yue Jin, Xin Hu, Min Yin, Xiaoju Men, Nan Chen, Chunhai Fan, Daniel T Chiu, Youzhong Wan, Changfeng Wu
Nanocavities composed of lipids and block polymers have demonstrated great potential in biomedical applications such as sensors, nanoreactors, and delivery vectors. However, it remains a great challenge to produce nanocavities from fluorescent semiconducting polymers owing to their hydrophobic rigid polymer backbones. Here, we describe a facile, yet general strategy that combines photocrosslinking with nanophase separation to fabricate multicolor, water-dispersible semiconducting polymer nanocavities (PNCs)...
April 22, 2018: Small
Feichin Hsiao, Po-Yang Huang, Takao Aoyagi, Shwu-Fen Chang, Jiahorng Liaw
The stability and bio-distribution of genes or drug complexes with poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO, Pluronic F-68) polymeric micelles (PM) are essential for an effective nanosized PM delivery system. We used Förster resonance energy transfer (FRET) pairs with PM and measured the FRET ratio to assess the stability of PM in vitro and in vivo on the cornea. The FRET ratio reached a plateau at 0.8 with 3% PM. Differential scanning calorimetry measurement confirmed the complex formation of FRET pairs with PM...
April 2018: Journal of Food and Drug Analysis
Xi Yang, Jun Zhang, Linmu Chen, Qiong Wu, Chao Yu
Chitosan oligosaccharides (COS), linear polymers of N-acetyl-D-glucosamine and deacetylated glucosamine, exhibit diverse pharmacological effects such as antimicrobial, antitumor, antioxidant and anti-inflammatory activities. Here, we explored their hypocholesterolemic effects in vivo and the molecular mechanisms of COS in hepatic cells. Our in vivo study of dyslipidemic ApoE-/- male mice showed that COS treatment of 500 mg kg-1 d-1 for 4 weeks clearly reduced the lipid deposits in the aorta and significantly decreased the hepatic proprotein convertase subtilisin/kexin type 9 (PCSK9) protein levels versus HFD groups (p < 0...
May 15, 2018: Experimental Cell Research
Robert Howlett, Katri Anttonen, Nicholas Read, Margaret C M Smith
Actinomycete bacteria use polyprenol phosphate mannose as a lipid linked sugar donor for extra-cytoplasmic glycosyl transferases that transfer mannose to cell envelope polymers, including glycoproteins and glycolipids. We showed recently that strains of Streptomyces coelicolor with mutations in the gene ppm1 encoding polyprenol phosphate mannose synthase were both resistant to phage φC31 and have greatly increased susceptibility to antibiotics that mostly act on cell wall biogenesis. Here we show that mutations in the genes encoding enzymes that act upstream of Ppm1 in the polyprenol phosphate mannose synthesis pathway can also confer phage resistance and antibiotic hyper-susceptibility...
April 2018: Microbiology
Pratheppa Rajagopal, Sowmiya Duraiswamy, Swaminathan Sethuraman, Jayandharan Giridhara Rao, Uma Maheswari Krishnan
The advantages and critical aspects of nanodimensional polymer-coated viral vector systems potentially applicable for gene delivery are reviewed. Various viral and nonviral vectors have been explored for gene therapy. Viral gene transfer methods, although highly efficient, are limited by their immunogenicity. Nonviral vectors have a lower transfection efficiency as a result of their inability to escape from the endosome. To overcome these drawbacks, novel nanotechnology-mediated interventions that involve the coating or modification of virus using polymers have emerged as a new paradigm in gene therapy...
April 2018: Journal of Gene Medicine
I Fernandez-Piñeiro, A Pensado, I Badiola, A Sanchez
Glycosaminoglycans (GAGs) are natural polymers that are broadly used in gene delivery systems to increase stability as well as decrease toxicity and nonspecific interactions, thereby increasing transfection efficiency. In this work, we propose sorbitan ester-based lipid nanoparticles (SENS) functionalised with the GAGs chondroitin sulfate (CS) and hyaluronic acid (HA) as gene delivery systems. For this purpose, we describe the design and evaluation of these nanosystems loaded with plasmid DNA, including an evaluation of their physicochemical characteristics, stability properties, ability to protect and efficiently transfect cells with Enhanced Green Fluorescent Protein plasmid (pEGFP) in vitro, and biocompatibility both in vitro and in vivo...
April 2018: European Journal of Pharmaceutics and Biopharmaceutics
Chi Zhang, Jinkai Ji, Xiaoyan Shi, Xiaoyu Zheng, Xuewei Wang, Fude Feng
Water-soluble conjugated polymers (WCPs) have prospective applications in the field of bioimaging, disease diagnosis, and therapy. However, the use of WCPs with controllability and regioregularity for bioapplications have scarcely been reported. In this work, we synthesized polythiophenes containing ester side chains (P3ET) via Kumada catalyst-transfer polycondensation (KCTP) and confirmed a quasi-"living" chain-growth mechanism. In addition, we obtained cationic regioregular polythiophenes (cPTs) by aminolysis of P3ET with varied chain lengths, and studied DNA binding capability and gene delivery performance...
February 7, 2018: ACS Applied Materials & Interfaces
Liqing Jin, Qing Cai, Wenlin Huang, Keyvan Dastmalchi, Joan Rigau, Marisa Molinas, Mercè Figueras, Olga Serra, Ruth E Stark
Potato native and wound healing periderms contain an external multilayered phellem tissue (potato skin) consisting of dead cells whose cell walls are impregnated with suberin polymers. The phellem provides physical and chemical barriers to tuber dehydration, heat transfer, and pathogenic infection. Previous RNAi-mediated gene silencing studies in native periderm have demonstrated a role for a feruloyl transferase (FHT) in suberin biosynthesis and revealed how its down-regulation affects both chemical composition and physiology...
March 2018: Phytochemistry
Pratyawadee Singhsa, Diana Diaz-Dussan, Hathaikarn Manuspiya, Ravin Narain
Cationic glycopolymers have shown to be excellent candidates for the fabrication of gene delivery devices due to their ability to electrostatically interact with negatively charged nucleic acids and the carbohydrate residues ensure enhanced stability and low toxicity of the polyplexes. The ability to engineer the polymers for optimized compositions, molecular weights, and architectures is critical in the design of effective gene delivery vehicles. Therefore, in this study, the aqueous reversible addition-fragmentation chain transfer polymerization (RAFT) was used to synthesize well-defined cationic glycopolymers with various cationic segments...
January 8, 2018: Biomacromolecules
Zhe Tan, Yogesh K Dhande, Theresa M Reineke
A series of 3-guanidinopropyl methacrylamide (GPMA)-based polymeric gene delivery vehicles were developed via aqueous reversible addition-fragmentation chain transfer (RAFT) polymerization. The polymers have been evaluated for their cellular internalization ability, transfection efficiency, and cytotoxicity. Two homopolymers: P(GPMA20 ), P(GPMA34 ), were synthesized to study the effect of guanidium polymer length on delivery efficiency and toxicity. In addition, an N-acetyl-d-galactosamine (GalNAc)-based hydrophilic block was incorporated to produce diblock polymers, which provides a neutral hydrophilic block that sterically protects plasmid-polymer complexes (polyplexes) from colloidal aggregation and aids polyplex targeting to hepatocytes via binding to asialoglycoprotein receptors (ASGPRs)...
December 20, 2017: Bioconjugate Chemistry
Sarah Urnauer, Andrea M Müller, Christina Schug, Kathrin A Schmohl, Mariella Tutter, Nathalie Schwenk, Wolfgang Rödl, Stephan Morys, Michael Ingrisch, Jens Bertram, Peter Bartenstein, Dirk-André Clevert, Ernst Wagner, Christine Spitzweg
Liver metastases present a serious problem in the therapy of advanced colorectal cancer (CRC), as more than 20% of patients have distant metastases at the time of diagnosis with less than 5% being cured. Consequently, new therapeutic approaches are of major need together with high-resolution imaging methods that allow highly specific detection of small metastases. The unique combination of reporter and therapy gene function of the sodium iodide symporter (NIS) may represent a promising theranostic strategy for CRC liver metastases allowing non-invasive imaging of functional NIS expression and therapeutic application of131 I...
November 3, 2017: Oncotarget
Kisuk Yang, Jin Young Oh, Jong Seung Lee, Yoonhee Jin, Gyeong-Eon Chang, Soo Sang Chae, Eunji Cheong, Hong Koo Baik, Seung-Woo Cho
Optoelectrical manipulation has recently gained attention for cellular engineering; however, few material platforms can be used to efficiently regulate stem cell behaviors via optoelectrical stimulation. In this study, we developed nanoweb substrates composed of photoactive polymer poly(3-hexylthiophene) (P3HT) to enhance the neurogenesis of human fetal neural stem cells (hfNSCs) through photo-induced electrical stimulation. METHODS: The photoactive nanoweb substrates were fabricated by self-assembled one-dimensional (1D) P3HT nanostructures (nanofibrils and nanorods)...
2017: Theranostics
C Campa, C E Gallenga, E Bolletta, P Perri
BACKGROUND: Gene therapy represents the therapeutic delivery of nucleic acid polymers into patient cells with the aim of treating an underlying disease. Over the past 2 decades this new therapy has made substantial progress owing to better understanding of the pathobiologic basis of various diseases coupled with growth of gene transfer biotechnologies. The eye, in particular, represents a suitable target for such therapy due to the immune privilege provided by the blood-ocular barrier, the ability to directly visualize, access and locally treat the cells and the minimal amount of vector needed given the size of this organ...
2017: Current Gene Therapy
Jonathan O'Keeffe Ahern, Sigen A, Dezhong Zhou, Yongsheng Gao, Jing Lyu, Zhao Meng, Lara Cutlar, Luca Pierucci, Wenxin Wang
Using a combined synthesis approach comprising reversible addition fragmentation transfer (RAFT) polymerization and ring opening reaction (ROR), a series of poly glycidyl methacrylate (polyGMA) polymers were designed and synthesized for gene delivery. These polymers characterised by low cationic charge respective to established gene delivery vectors such as PEI were studied to further elucidate the key structure activity parameters which mediate efficient and biocompatible gene delivery. Compared to PEI these brush-like polymers facilitated markedly improved safety and gene delivery efficiency...
November 10, 2017: Biomacromolecules
Liyu Chen, Joshua D Simpson, Adrian V Fuchs, Barbara E Rolfe, Kristofer J Thurecht
Nanoscaled polymeric materials are increasingly being investigated as pharmaceutical products, drug/gene delivery vectors, or health-monitoring devices. Surface charge is one of the dominant parameters that regulates nanomaterial behavior in vivo. In this paper, we demonstrated how control over chemical synthesis allowed manipulation of nanoparticle surface charge, which in turn greatly influenced the in vivo behavior. Three methacrylate/methacrylamide-based monomers were used to synthesize well-defined hyperbranched polymers (HBP) by reversible addition-fragmentation chain transfer (RAFT) polymerization...
December 4, 2017: Molecular Pharmaceutics
Ekaterina S Lisitsyna, Tiia-Maaria Ketola, Emmanuelle Morin-Picardat, Huamin Liang, Martina Hanzlíková, Arto Urtti, Marjo Yliperttula, Elina Vuorimaa-Laukkanen
Structural dynamics of the polyethylenimine-DNA and poly(l-lysine)-DNA complexes (polyplexes) was studied by steady-state and time-resolved fluorescence spectroscopy using the fluorescence resonance energy transfer (FRET) technique. During the formation of the DNA polyplexes, the negative phosphate groups (P) of DNA are bound by the positive amine groups (N) of the polymer. At N/P ratio 2, nearly all of the DNA's P groups are bound by the polymer N groups: these complexes form the core of the polyplexes. The excess polymer, added to this system to increase the N/P ratio to the values giving efficient gene delivery, forms a positively charged shell around the core polyplex...
December 7, 2017: Journal of Physical Chemistry. B
Elizabeth G L Williams, Oliver E Hutt, Tracey M Hinton, Sophie C Larnaudie, Tam Le, James M MacDonald, Pathiraja Gunatillake, San H Thang, Peter J Duggan
Achieving efficient and targeted delivery of short interfering (siRNA) is an important research challenge to overcome to render highly promising siRNA therapies clinically successful. Challenges exist in designing synthetic carriers for these RNAi constructs that provide protection against serum degradation, extended blood retention times, effective cellular uptake through a variety of uptake mechanisms, endosomal escape, and efficient cargo release. These challenges have resulted in a significant body of research and led to many important findings about the chemical composition and structural layout of the delivery vector for optimal gene silencing...
December 11, 2017: Biomacromolecules
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