Browse
Submit Data
Databases
API
Help

Dataset Information

23 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Multi-armed cationic cyclodextrin:poly(ethylene glycol) polyrotaxanes as efficient gene silencing vectors.

ABSTRACT: A family of branched polyrotaxanes (bPRTx(+)), threaded with multiple cationic ?-cyclodextrins (?-CDs) onto a multi-armed poly(ethylene glycol) (PEG) core, were synthesized and studied as gene silencing vectors. These bPRTx(+) formed stable, positively charged complexes with diameters of 150-250 nm at N/P ratios as low as 2.5. The bPRTx(+) materials were shown to have gene-silencing efficiencies comparable to those of Lipofectamine 2000 (L2k) and bPEI, while displaying similar toxicity profiles. The unique structure of these polyrotaxanes allows them to effectively condense and complex siRNA into nanoparticles at much lower N/P ratios than L2k or bPEI. These findings suggest that bPRTx(+) may be useful materials for gene therapy applications.

SUBMITTER: Kulkarni A

PROVIDER: S-EPMC3524380 | biostudies-other | 2013 Jan

REPOSITORIES: biostudies-other

ACCESS DATA

Json Xml

Publications

Multi-armed cationic cyclodextrin:poly(ethylene glycol) polyrotaxanes as efficient gene silencing vectors.

Kulkarni Aditya A DeFrees Kyle K Schuldt Ryan A RA Vlahu Alexander A VerHeul Ross R Hyun Seok-Hee SH Deng Wei W Thompson David H DH

Integrative biology : quantitative biosciences from nano to macro 20130101 1

A family of branched polyrotaxanes (bPRTx(+)), threaded with multiple cationic α-cyclodextrins (α-CDs) onto a multi-armed poly(ethylene glycol) (PEG) core, were synthesized and studied as gene silencing vectors. These bPRTx(+) formed stable, positively charged complexes with diameters of 150-250 nm at N/P ratios as low as 2.5. The bPRTx(+) materials were shown to have gene-silencing efficiencies comparable to those of Lipofectamine 2000 (L2k) and bPEI, while displaying similar toxicity profiles. ...[more]

PMID: 23042106

Similar Datasets

Cationic ?-cyclodextrin:poly(ethylene glycol) polyrotaxanes for siRNA delivery.

Project description:RNA interference has broad therapeutic potential due to its high specificity and ability to potentially evade drug resistance. Three cationic ?-cyclodextrin:poly(ethylene glycol) polyrotaxanes derived from polymer axles of different sizes (MW 2,000, 3,400, and 10,000) have been synthesized for delivering siRNA. These polyrotaxanes are able to condense siRNA into positively charged particles that are <200 nm in diameter, enabling their facile internalization into mammalian cells. The cationic polyrotaxanes display cytotoxicity profiles that are >10(2)-fold lower than the commercial standard bPEI and gene silencing efficiencies that are comparable to those of both Lipofectamine 2000 and bPEI. Our findings suggest that the cationic polyrotaxanes display a size-activity relationship, wherein the higher molecular weight polyrotaxanes (PEG3,400 and 10,000) are able to condense and deliver siRNA better than the lower molecular weight material (PEG2,000).

| S-EPMC4083495 | biostudies-literature

Poly (ethylene glycol)-armed hyperbranched polyoxetanes for anticancer drug delivery.

Project description:A facile method for synthesis of polyethylene glycol (PEG)-armed hyperbranched polyoxetanes is presented as well as characterization and use in drug delivery. A series of hyperbranched polyoxetanes with multiple PEG arms were synthesized via a one-pot cationic ring-opening polymerization of 3-ethyl-3-hydroxymethyloxetane (EHMO) and its PEGylated derivative (EPMO), in which the feed mass ratio of EHMO to EPMO was 98:2, 96:4, 74:26, or 17:83. Characterization methods included NMR, DLS, FT-IR, DSC, and SEM. Toxicity of the synthesized polymers to human dermal fibroblasts was evaluated using the MTT assay. Formulation into particles was carried out to encapsulate the anticancer drug camptothecin using the single oil-in-water (o/w) solvent evaporation method. The resulting drug encapsulated particles were evaluated for antitumor activity using HN12 cells.

| S-EPMC3513288 | biostudies-literature

Photoresponsive Gelation of Four-Armed Poly(ethylene glycol) with Photodimerizable Groups.

Project description:Standard hydrogels prepared by free radical polymerization (FRP) have heterogeneous structures with a wide mesh size distribution, which affect their mechanical and separation properties. Recent research has identified four-armed poly(ethylene glycol) (tetra-PEG) as a solution to this problem. tetra-PEG gels with a homogeneous network can be prepared and applied as high-strength gels and cell-culture substrates by reacting two types of tetra-PEG with different reactive groups at the ends. In this study, we report a photoresponsive tetra-PEG that undergoes a phase transition from a sol to a gel state in response to light. tetra-PEGs containing cinnamoyl and maleimide groups at the ends of the four-armed chains were found to gel when exposed to light. The effects of polymer concentration and light irradiation time on the gelation of tetra-PEG containing photodimerization groups were investigated. The results showed that the elastic modulus of the gel increased with the increase in the light irradiation time.

| S-EPMC8950757 | biostudies-literature

Verteporfin-Loaded Poly(ethylene glycol)-Poly(beta-amino ester)-Poly(ethylene glycol) Triblock Micelles for Cancer Therapy.

Project description:Amphiphilic polymers can be used to form micelles to deliver water-insoluble drugs. A biodegradable poly(ethylene glycol) (PEG)-poly(beta-amino ester) (PBAE)-PEG triblock copolymer was developed that is useful for drug delivery. It was shown to successfully encapsulate and pH-dependently release a water-insoluble, small molecule anticancer drug, verteporfin. PEG-PBAE-PEG micelle morphology was also controlled through variations to the hydrophobicity of the central PBAE block of the copolymer in order to evade macrophage uptake. Spherical micelles were 50 nm in diameter, while filamentous micelles were 31 nm in width with an average aspect ratio of 20. When delivered to RAW 264.7 mouse macrophages, filamentous micelles exhibited a 89% drop in cellular uptake percentage and a 5.6-fold drop in normalized geometric mean cellular uptake compared to spherical micelles. This demonstrates the potential of high-aspect-ratio, anisotropically shaped PEG-PBAE-PEG micelles to evade macrophage-mediated clearance. Both spherical and filamentous micelles also showed therapeutic efficacy in human triple-negative breast cancer and small cell lung cancer cells without requiring photodynamic therapy to achieve an anticancer effect. Both spherical and filamentous micelles were more effective in killing lung cancer cells than breast cancer cells at equivalent verteporfin concentrations, while spherical micelles were shown to be more effective than filamentous micelles against both cancer cells. Spherical and filamentous micelles at 5 and 10 ?M respective verteporfin concentration resulted in 100% cell killing of lung cancer cells, but both micelles required a higher verteporfin concentration of 20 ?M to kill breast cancer cells at the levels of 80% and 50% respectively. This work demonstrates the potential of PEG-PBAE-PEG as a biodegradable, anisotropic drug delivery system as well as the in vitro use of verteporfin-loaded micelles for cancer therapy.

| S-EPMC6249031 | biostudies-literature

Physicochemical characteristics of pH-sensitive poly(L-histidine)-b-poly(ethylene glycol)/poly(L-lactide)-b-poly(ethylene glycol) mixed micelles.

Project description:A novel pH-sensitive polymeric micellar system composed of poly(L-histidine)-b-poly(ethylene glycol) and poly(L-lactide)-b-poly(ethylene glycol) block copolymers was studied by dynamic/static light scattering, spectrofluorimetry and differential scanning calorimetry. The mixed micelles displayed ultra Ph Sensitivity Which Could Be Tuned By Varying The Mixing Ratio Of The Two Polymers. In Particular, Mixed Micelles Composed Of 25 Wt.% Poly(L-lactide)-b-poly(ethylene glycol) exhibited desirable pH dependency which could be used as a drug delivery system that selectively targeted the extracellular pH of acidic solid tumors. Micelles were quite stable from pH 7.4 to 7.0 but underwent a two-stage destabilization as pH decreased further. A significant increase in size and aggregation number was observed when pH dropped to 6.8. Further disruption of the micelle core eventually caused phase separation in the micelle core and dissociation of ionized poly(L-histidine)-b-poly(ethylene glycol) molecules from the micelles as pH decreased to 6.0. Increased electrostatic repulsions which arise from the progressive protonation of imidazole rings overwhelming the hydrophobic interactions among uncharged neutral blocks is considered to be the mechanism for destabilization of the micelle core.

| S-EPMC2276666 | biostudies-literature

Pendant polymer:amino-?-cyclodextrin:siRNA guest:host nanoparticles as efficient vectors for gene silencing.

Project description:A novel siRNA delivery vector has been developed, based on the self-assembly of monosubstituted cationic ?-CD derivatives with a poly(vinyl alcohol)MW27kD (PVA) main-chain polymer bearing poly(ethylene glycol)MW2000 (PEG) and acid-labile cholesterol-modified (Chol) grafts through an acid-sensitive benzylidene acetal linkage. These components were investigated for their ability to form nanoparticles with siRNA using two different assembly schemes, involving either precomplexation of the pendant Chol-PVA-PEG polymer with the cationic ?-CD derivatives before siRNA condensation or siRNA condensation with the cationic ?-CD derivatives prior to addition of Chol-PVA-PEG to engage host:guest complexation. The pendant polymer:amino-?-CD:siRNA complexes were shown to form nanoparticles in the size range of 120-170 nm, with a slightly negative zeta potential. Cell viability studies in CHO-GFP cells shows that these materials have 10(3)-fold lower cytotoxicities than 25 kD bPEI, while maintaining gene-silencing efficiencies that are comparable to those of benchmark transfection reagents such as bPEI and Lipofectamine 2000. These results suggest that the degradable Chol-PVA-PEG polymer is able to self-assemble in the presence of siRNA and cationic-?-CD to form nanoparticles that are an effective and low-toxicity vehicle for delivering siRNA cargo to target cells.

| S-EPMC6885381 | biostudies-literature

Bottlebrush-architectured poly(ethylene glycol) as an efficient vector for RNA interference in vivo.

Project description:Nonhepatic delivery of small interfering RNAs (siRNAs) remains a challenge for development of RNA interference-based therapeutics. We report a noncationic vector wherein linear poly(ethylene glycol) (PEG), a polymer generally considered as inert and safe biologically but ineffective as a vector, is transformed into a bottlebrush architecture. This topology provides covalently embedded siRNA with augmented nuclease stability and cellular uptake. Consisting almost entirely of PEG and siRNA, the conjugates exhibit a ~25-fold increase in blood elimination half-life and a ~19-fold increase in the area under the curve compared with unmodified siRNA. The improved pharmacokinetics results in greater tumor uptake and diminished liver capture. Despite the structural simplicity these conjugates efficiently knock down target genes in vivo without apparent toxic and immunogenic reactions. Given the benign biological nature of PEG and its widespread precedence in biopharmaceuticals, we anticipate the brush polymer-based technology to have a significant impact on siRNA therapeutics.

| S-EPMC6382396 | biostudies-literature

Photoclick Hydrogels Prepared from Functionalized Cyclodextrin and Poly(ethylene glycol) for Drug Delivery and in Situ Cell Encapsulation.

Project description:Polymers or hydrogels containing modified cyclodextrin (CD) are highly useful in drug delivery applications, as CD is a cytocompatible amphiphilic molecule that can complex with a variety of hydrophobic drugs. Here, we designed modular photoclick thiol-ene hydrogels from derivatives of ?CD and poly(ethylene glycol) (PEG), including ?CD-allylether (?CD-AE), ?CD-thiol (?CD-SH), PEG-thiol (PEGSH), and PEG-norbornene (PEGNB). Two types of CD-PEG hybrid hydrogels were prepared using radical-mediated thiol-ene photoclick reactions. Specifically, thiol-allylether hydrogels were formed by reacting multiarm PEGSH and ?CD-AE, and thiol-norbornene hydrogels were formed by cross-linking ?CD-SH and multiarm PEGNB. We characterized the properties of these two types of thiol-ene hydrogels, including gelation kinetics, gel fractions, hydrolytic stability, and cytocompatibility. Compared with thiol-allylether hydrogels, thiol-norbornene photoclick reaction formed hydrogels with faster gelation kinetics at equivalent macromer contents. Using curcumin, an anti-inflammatory and anticancer hydrophobic molecule, we demonstrated that CD-cross-linked PEG-based hydrogels, when compared with pure PEG-based hydrogels, afforded higher drug loading efficiency and prolonged delivery in vitro. Cytocompatibility of these CD-cross-linked hydrogels were evaluated by in situ encapsulation of radical sensitive pancreatic MIN6 ?-cells. All formulations and cross-linking conditions tested were cytocompatible for cell encapsulation. Furthermore, hydrogels cross-linked by ?CD-SH showed enhanced cell proliferation and insulin secretion as compared to gels cross-linked by either dithiothreitol (DTT) or ?CD-AE, suggesting the profound impact of both macromer compositions and gelation chemistry on cell fate in chemically cross-linked hydrogels.

| S-EPMC5450649 | biostudies-literature

Poly(Ethylene Glycol)/β-Cyclodextrin Pseudorotaxane Complexes as Sustainable Dispersing and Retarding Materials in a Cement-Based Mortar.

Project description:Pseudorotaxane complexes between β-CD and mPEG derivatives bearing a carboxylic acid function (mPEG-COOH) were synthesized and investigated for their dispersing properties in a cement-based mortar. The formation of mPEG-COOH derivatives and their pseudorotaxanes was investigated by 1D nuclear magnetic resonance, diffusion ordered spectroscopy, and thermogravimetric analysis experiments. Mortar tests clearly indicate that mPEG-COOH@β-CD-interpenetrated supramolecules show excellent dispersing abilities. In addition, the supramolecular complexes show a retarding effect, analogously to other known β-CD-based superplasticizers in which the β-CD is covalently grafted on a polymeric backbone.

| S-EPMC8154154 | biostudies-literature

Biodegradable Poly (lactic acid)/ Poly (ethylene glycol) Reinforced Multi-Walled Carbon Nanotube Nanocomposite Fabrication, Characterization, Properties, and Applications.

Project description:This paper presents the electromagnetic interference properties of multi-walled carbon nanotubes (MWCNTs) as a novel nano-reinforcement filler in poly (lactic acid) (PLA)/poly (ethylene glycol) (PEG) polymer matrix that was prepared via melt blending mode. Plasticization of PLA was first carried out by PEG, which overcomes its brittleness problem, in order to enhance its flexibility. A waveguide adapter technique was used to measure the dielectric properties ?r, and S-parameters reflection (S11) and transmission (S21) coefficients. The dielectric properties, microwave attenuation performances, and electromagnetic interference shielding effectiveness (EMISE) for all the material under test have been calculated over the full X-Band (8-12 GHz) due to its importance for military and commercial applications. The prepared samples were studied while using X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), Fourier transforms infrared spectroscopy (FTIR), mechanical properties measurements, as well as thermogravimetric analysis (TGA). The results showed that the dielectric properties increased with increased multi-walled carbon nanotubes (MWCNTs) filler, as well as the shielding effectiveness of the MWCNT/PLA/PEG nanocomposites increased with the increasing of MWCNTs. The highest SE total value was found to be 42.07 dB at 12 GHz for 4 wt% filler content. It is also observed that the attenuation values of the nanocomposites increased with an increase in MWCNTs loading, as well as the power loss values for all of the samples increased with the increase in MWCNTs loading, except the amount of the transmitted wave through the nanocomposites.

| S-EPMC7077650 | 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