Browse
Submit Data
Databases
API
Help

Dataset Information

23 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Functional Polyglycidol-Based Block Copolymers for DNA Complexation.

ABSTRACT: Gene therapy is an attractive therapeutic method for the treatment of genetic disorders for which the efficient delivery of nucleic acids into a target cell is critical. The present study is aimed at evaluating the potential of copolymers based on linear polyglycidol to act as carriers of nucleic acids. Functional copolymers with linear polyglycidol as a non-ionic hydrophilic block and a second block bearing amine hydrochloride pendant groups were prepared using previously synthesized poly(allyl glycidyl ether)-b-polyglycidol block copolymers as precursors. The amine functionalities were introduced via highly efficient radical addition of 2-aminoethanethiol hydrochloride to the alkene side groups. The modified copolymers formed loose aggregates with strongly positive surface charge in aqueous media, stabilized by the presence of dodecyl residues at the end of the copolymer structures and the hydrogen-bonding interactions in polyglycidol segments. The copolymer aggregates were able to condense DNA into stable and compact nanosized polyplex particles through electrostatic interactions. The copolymers and the corresponding polyplexes showed low to moderate cytotoxicity on a panel of human cancer cell lines. The cell internalization evaluation demonstrated the capability of the polyplexes to successfully deliver DNA into the cancer cells.

SUBMITTER: Kalinova R

PROVIDER: S-EPMC8431755 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Polyelectrolyte Complexation of Oligonucleotides by Charged Hydrophobic-Neutral Hydrophilic Block Copolymers.

Project description:Polyelectrolyte complex micelles (PCMs, core-shell nanoparticles formed by complexation of a polyelectrolyte with a polyelectrolyte-hydrophilic neutral block copolymer) offer a solution to the critical problem of delivering therapeutic nucleic acids, Despite this, few systematic studies have been conducted on how parameters such as polycation charge density, hydrophobicity, and choice of charged group influence PCM properties, despite evidence that these strongly influence the complexation behavior of polyelectrolyte homopolymers. In this article, we report a comparison of oligonucleotide PCMs and polyelectrolyte complexes formed by poly(lysine) and poly((vinylbenzyl) trimethylammonium) (PVBTMA), a styrenic polycation with comparatively higher charge density, increased hydrophobicity, and a permanent positive charge. All of these differences have been individually suggested to provide increased complex stability, but we find that PVBTMA in fact complexes oligonucleotides more weakly than does poly(lysine), as measured by stability versus added salt. Using small angle X-ray scattering and electron microscopy, we find that PCMs formed from both cationic blocks exhibit very similar structure-property relationships, with PCM radius determined by the cationic block size and shape controlled by the hybridization state of the oligonucleotides. These observations narrow the design space for optimizing therapeutic PCMs and provide new insights into the rich polymer physics of polyelectrolyte self-assembly.

| S-EPMC6402004 | biostudies-literature

Cell Engineering with Functional Poly(oxanorbornene) Block Copolymers.

Project description:Cell-based therapies are gaining prominence in treating a wide variety of diseases and using synthetic polymers to manipulate these cells provides an opportunity to impart function that could not be achieved using solely genetic means. Herein, we describe the utility of functional block copolymers synthesized by ring-opening metathesis polymerization (ROMP) that can insert directly into the cell membrane via the incorporation of long alkyl chains into a short polymer block leading to non-covalent, hydrophobic interactions with the lipid bilayer. Furthermore, we demonstrate that these polymers can be imbued with advanced functionalities. A photosensitizer was incorporated into these polymers to enable spatially controlled cell death by the localized generation of 1 O2 at the cell surface in response to red-light irradiation. In a broader context, we believe our polymer insertion strategy could be used as a general methodology to impart functionality onto cell-surfaces.

| S-EPMC7482174 | biostudies-literature

Temperature- and Composition-Dependent DNA Condensation by Thermosensitive Block Copolymers.

Project description:Successful intracellular delivery of genes requires an efficient carrier, as genes by themselves cannot diffuse across cell membranes. Because of the toxicity and immunogenicity of viral vectors, nonviral vectors are gaining tremendous interest in research. In this work, we have investigated the temperature-dependent DNA condensation efficiency of various compositions of a thermosensitive block copolymer viz., poly(N-isopropylacrylamide)-b-poly(2-(diethylamino)ethyl methacrylate) (PNIPA-b-PDMAEMA). Three different copolymer compositions of varying molecular weights were successfully synthesized via the RAFT polymerization technique. Steady-state fluorescence and circular dichroism (CD) spectroscopies, dynamic light scattering (DLS) and zeta potential measurements, agarose gel electrophoresis, and atomic force microscopy techniques were utilized to study the interaction of the copolymers with DNA at temperatures above and below the critical aggregation temperature (CAT). All these experiments revealed that, above the CAT, there was formation of highly stable and tight polymer-DNA complexes (polyplexes). The size of polyplexes was dependent on the temperature up to a certain charge ratio, as determined by the DLS results. The results obtained from temperature-dependent fluorescence spectroscopy, CD, and gel electrophoresis indicated that the DNA molecules were shielded more from aqueous exposure above the CAT because of the formation of relatively more compact complexes. The polyplexes also exhibited changes in the particle morphology below and above the CAT, with particles generated above CAT being more spherical in morphology. These results suggested at the possibility of modulating the complex formation by temperature modification. The present biophysical studies would provide new physical insight into the design of novel gene carriers.

| S-EPMC6045361 | biostudies-literature

Intracellular trafficking of polyamidoamine-poly(ethylene glycol) block copolymers in DNA delivery.

Project description:The delivery of nucleic acids has the potential to revolutionize medicine by allowing previously untreatable diseases to be clinically addressed. Viral delivery systems have shown immunogenicity and toxicity dangers, but synthetic vectors have lagged in transfection efficiency. Previously, we developed a modular, linear-dendritic block copolymer architecture with high gene transfection efficiency compared to commercial standards. This rationally designed system makes use of a cationic dendritic block to condense the anionic DNA and forms complexes with favorable endosomal escape properties. The linear block provides biocompatibility and protection from serum proteins, and can be functionalized with a targeting ligand. In this work, we quantitate performance of this system with respect to intracellular barriers to gene delivery using both high-throughput and traditional approaches. An image-based, high-throughput assay for endosomal escape is described and applied to the block copolymer system. Nuclear entry is demonstrated to be the most significant barrier to more efficient delivery and will be addressed in future versions of the system.

| S-EPMC3218102 | biostudies-literature

Functional Modification of Silica through Enhanced Adsorption of Elastin-Like Polypeptide Block Copolymers.

Project description:A powerful tool for controlling interfacial properties and molecular architecture relies on the tailored adsorption of stimuli-responsive block copolymers onto surfaces. Here, we use computational and experimental approaches to investigate the adsorption behavior of thermally responsive polypeptide block copolymers (elastin-like polypeptides, ELPs) onto silica surfaces, and to explore the effects of surface affinity and micellization on the adsorption kinetics and the resultant polypeptide layers. We demonstrate that genetic incorporation of a silica-binding peptide (silaffin R5) results in enhanced adsorption of these block copolymers onto silica surfaces as measured by quartz crystal microbalance and ellipsometry. We find that the silaffin peptide can also direct micelle adsorption, leading to close-packed micellar arrangements that are distinct from the sparse, patchy arrangements observed for ELP micelles lacking a silaffin tag, as evidenced by atomic force microscopy measurements. These experimental findings are consistent with results of dissipative particle dynamics simulations. Wettability measurements suggest that surface immobilization hampers the temperature-dependent conformational change of ELP micelles, while adsorbed ELP unimers (i.e., unmicellized block copolymers) retain their thermally responsive property at interfaces. These observations provide guidance on the use of ELP block copolymers as building blocks for fabricating smart surfaces and interfaces with programmable architecture and functionality.

| S-EPMC5809277 | biostudies-literature

Biocompatible, degradable thermoplastic polyurethane based on polycaprolactone-block-polytetrahydrofuran-block-polycaprolactone copolymers for soft tissue engineering.

Project description:Biodegradable synthetic polymers have been widely used as tissue engineering scaffold materials. Even though they have shown excellent biocompatibility, they have failed to resemble the low stiffness and high elasticity of soft tissues because of the presence of massive rigid ester bonds. Herein, we synthesized a new thermoplastic polyurethane elastomer (CTC-PU(BET)) using poly ester ether triblock copolymer (polycaprolactone-block-polytetrahydrofuran-block-polycaprolactone triblock copolymer, PCTC) as the soft segment, aliphatic diisocyanate (hexamethylene diisocyanate, HDI) as the hard segment, and degradable diol (bis(2-hydroxyethyl) terephthalate, BET) as the chain extender. PCTC inhibited crystallization and reduced the melting temperature of CTC-PU(BET), and BET dramatically enhanced the thermal decomposition and hydrolytic degradation rate when compared with conventional polyester-based biodegradable TPUs. The CTC-PU(BET) synthesized in this study possessed a low tensile modulus and tensile strength of 2.2 MPa and 1.3 MPa, respectively, and an elongation-at-break over 700%. Meanwhile, it maintained a 95.3% recovery rate and 90% resilience over ten cycles of loading and unloading. In addition, the TPU could be electrospun into both random and aligned fibrous scaffolds consisting of major microfibers and nanobranches. 3T3 fibroblast cell culture confirmed that these scaffolds outperformed the conventional biodegradable TPU scaffolds in terms of substrate-cellular interactions and cell proliferation. Considering the advantages of this TPU, such as ease of synthesis, low cost, low stiffness, high elasticity, controllable degradation rate, ease of processability, and excellent biocompatibility, it has great prospects to be used as a tissue engineering scaffold material for soft tissue regeneration.

| S-EPMC5695921 | biostudies-literature

Amphiphilic block copolymers enhance cellular uptake and nuclear entry of polyplex-delivered DNA.

Project description:This work for the first time demonstrates that synthetic polymers enhance uptake and nuclear import of plasmid DNA (pDNA) through the activation of cellular trafficking machinery. Nonionic block copolymers of poly(ethylene oxide) and poly(propylene oxide), Pluronics, are widely used as excipients in pharmaceutics. We previously demonstrated that Pluronics increase the phosphorylation of IkappaB and subsequent NFkappaB nuclear localization as well as upregulate numerous NFkappaB-related genes. In this study, we show that Pluronics enhance gene transfer by pDNA/polycation complexes ("polyplexes") in a promoter-dependent fashion. Addition of Pluronic P123 or P85 to polyethyleneimine-based polyplexes had little effect on polyplex particle size but significantly enhanced pDNA cellular uptake, nuclear translocation, and gene expression in several cell lines. When added to polyplex-transfected cells after transfection, Pluronics enhanced nuclear import of pDNA containing NFkappaB binding sites, but have no effect on import of pDNA without these sites. Altogether, our studies suggest that Pluronics rapidly activate NFkappaB, which binds cytosolic pDNA that possesses promoters containing NFkappaB binding sites and consequently increase nuclear import of pDNA through NFkappaB nuclear translocation.

| S-EPMC2574534 | biostudies-literature

Functional Block Copolymers Carrying One Double-Stranded Ladderphane and One Single-Stranded Block in a Facile Metathesis Cyclopolymerization Procedure.

Project description:In order to improve the poor film-forming ability of polymeric ladderphane, di-block copolymers containing perylene diimide (PDI)-linked double-stranded poly(1,6-heptadiyne) ladderphane and branched alkyl side chains modified single-stranded poly(1,6-heptadiyne) were synthesized by metathesis cyclopolymerization (MCP) using Grubbs third-generation catalyst (Ru-III) in tetrahydrofuran solvent. The first block containing the ladderphane structure leads to higher thermal-stability, wider UV-vis absorption, lower LUMO level and ladderphane-induced rigidity and poor film-forming ability. The second block containing long alkyl chains is crucial for the guarantee of excellent film-forming ability. By comparing the effect of ladderphane structure on the resulted copolymers, single-stranded poly(1,6-heptadiyne) derivatives with PDI pedant were also processed. The structures of copolymers were proved by 1H NMR and gel permeation chromatography, electrochemical, photophysical, and thermal-stability performance were achieved by cyclic voltammetry (CV), UV-visible spectroscopy and thermogravimetric analysis (TGA) measurements. According to the experiment results, both copolymers possessed outstanding film-forming ability, which cannot be realized by small PDI molecules and oligomers. And they can serve as a superior candidate as for n-type materials, especially for their relatively wide range of light absorption (λ = 200~800 nm), and lower LUMO level (-4.3 and -4.0 eV).

| S-EPMC6829535 | biostudies-literature

Supramolecular Block Copolymers under Thermodynamic Control.

Project description:Supramolecular block copolymers are becoming attractive materials in nascent optoelectronic and catalytic technologies. However, their dynamic nature precludes the straightforward tuning and analysis of the polymer's structure. Here we report the elucidation on the microstructure of triarylamine triamide-based supramolecular block copolymers through a comprehensive battery of spectroscopic, theoretical, and super-resolution microscopic techniques. Via spectroscopic analysis we demonstrate that the direct mixing of preassembled homopolymers and the copolymerization induced by slow cooling of monomers lead to the formation of the same copolymer's architecture. The small but pronounced deviation of the experimental spectra from the linear combination of the homopolymers' spectra hints at the formation of block copolymers. A mass balance model is introduced to further unravel the microstructure of the copolymers formed, and it confirms that stable multiblock supramolecular copolymers can be accessed from different routes. The multiblock structure of the supramolecular copolymers originates from the fine balance between favorable hydrogen-bonding interactions and a small mismatch penalty between two different monomers. Finally, we visualized the formation of the supramolecular block copolymers by adapting a recently developed super-resolution microscopy technique, interface point accumulation for imaging in nanoscale topography (iPAINT), for visualizing the architectures formed in organic media. Combining multiple techniques was crucial to unveil the microstructure of these complex dynamic supramolecular systems.

| S-EPMC6002778 | biostudies-literature

Moebius strips of chiral block copolymers.

Project description:The Moebius topology (twisted, single-sided strip) is intriguing because of its structural elegance and distinct properties. Here we report the generation of block copolymer Moebius strips via a fast self-assembly of chiral block copolymer polystyrene-block-poly(D-lactide acid) (PS-b-PDLA) in tetrahydrofuran/water mixed solvents. The Moebius strip is formed by morphological evolution from large compound micelle (LCM) to spindle-like micelle (SLM) and then to toroid with a 180° twist along the ring. Mechanism insight reveals that a subtle balance of crystallization of PDLA and microphase separation between PS and PDLA chains dominates the formation of Moebius strips. An intriguing helix-helix transition occurs during the chiral transfer from microphase to assemblies, which is driven by relaxation of the internal stress within SLM related to orientated stretching of PS chains. Mesoporous chiral channels can be generated within Moebius strips after removal of PDLA, which are interesting in chiral recognition, separation and asymmetric catalysis.

| S-EPMC6733789 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data