Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Non-viral gene delivery via membrane-penetrating, mannose-targeting supramolecular self-assembled nanocomplexes.

ABSTRACT: Supramolecular self-assembled nanocomplexes (SSANs) capable of mannose receptor-mediated endocytosis and permeable to cellular and endosomal membranes are developed via the assembly of multiple rationally designed, function-specific materials. As a unique non-viral gene delivery vector, SSANs outperform commercial transfection reagents, including LPF2000, PEI, and jetPEI, by up to 2 orders of magnitude.

SUBMITTER: Yin L

PROVIDER: S-EPMC3757134 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Non-viral gene delivery via membrane-penetrating, mannose-targeting supramolecular self-assembled nanocomplexes.

Yin Lichen L Song Ziyuan Z Kim Kyung Hoon KH Zheng Nan N Gabrielson Nathan P NP Cheng Jianjun J

Advanced materials (Deerfield Beach, Fla.) 20130218 22

Supramolecular self-assembled nanocomplexes (SSANs) capable of mannose receptor-mediated endocytosis and permeable to cellular and endosomal membranes are developed via the assembly of multiple rationally designed, function-specific materials. As a unique non-viral gene delivery vector, SSANs outperform commercial transfection reagents, including LPF2000, PEI, and jetPEI, by up to 2 orders of magnitude. ...[more]

PMID: 23417835

Similar Datasets

Self-Assembled Cationic Polypeptide Supramolecular Nanogels for Intracellular DNA Delivery.

Project description:Supramolecular nanogels are an emerging class of polymer nanocarriers for intracellular delivery, due to their straightforward preparation, biocompatibility, and capability to spontaneously encapsulate biologically active components such as DNA. A completely biodegradable three-component cationic supramolecular nanogel was designed exploiting the multivalent host-guest interaction of cyclodextrin and adamantane attached to a polypeptide backbone. While cyclodextrin was conjugated to linear poly-L-lysine, adamantane was grafted to linear as well as star shaped poly-L-lysine. Size control of nanogels was obtained with the increase in the length of the host and guest polymer. Moreover, smaller nanogels were obtained using the star shaped polymers because of the compact nature of star polymers compared to linear polymers. Nanogels were loaded with anionic model cargoes, pyranine and carboxyfluorescein, and their enzyme responsive release was studied using protease trypsin. Confocal microscopy revealed successful transfection of mammalian HeLa cells and intracellular release of pyranine and plasmid DNA, as quantified using a luciferase assay, showing that supramolecular polypeptide nanogels have significant potential in gene therapy applications.

| S-EPMC8457085 | biostudies-literature

Delivery of intact transcription factor by using self-assembled supramolecular nanoparticles.

Project description: Not available

| S-EPMC3088165 | biostudies-literature

iRGD-guided Tumor-penetrating Nanocomplexes for Therapeutic siRNA Delivery to Pancreatic Cancer.

Project description:Pancreatic cancer is one of the leading causes of cancer-related death, with 5-year survival of 8.5%. The lack of significant progress in improving therapy reflects our inability to overcome the desmoplastic stromal barrier in pancreatic ductal adenocarcinoma (PDAC) as well as a paucity of new approaches targeting its genetic underpinnings. RNA interference holds promise in targeting key mutations driving PDAC; however, a nucleic acid delivery vehicle that homes to PDAC and breaches the stroma does not yet exist. Noting that the cyclic peptide iRGD mediates tumor targeting and penetration through interactions with ?v?3/5 integrins and neuropilin-1, we hypothesized that "tandem" peptides combining a cell-penetrating peptide and iRGD can encapsulate siRNA to form tumor-penetrating nanocomplexes (TPN) capable of delivering siRNA to PDAC. The use of directly conjugated iRGD is justified by receptor expression patterns in human PDAC biopsies. In this work, we optimize iRGD TPNs with polyethylene glycol (PEG)-peptide conjugates for systemic delivery to sites of disease. We show that TPNs effectively knockdown siRNA targets in PDAC cell lines and in an immunocompetent genetically engineered mouse model of PDAC. Furthermore, we validate their tumor-penetrating ability in three-dimensional organoids and autochthonous tumors. In murine therapeutic trials, TPNs delivering anti-Kras siRNA significantly delay tumor growth. Thus, iRGD TPNs hold promise in treating PDAC by not only overcoming physical barriers to therapy, but by leveraging the stroma to achieve knockdown of the gold-standard genetic target. Moreover, the modular construction of this delivery platform allows for facile adaptation to future genetic target candidates in pancreatic cancer. Mol Cancer Ther; 17(11); 2377-88. ©2018 AACR.

| S-EPMC6298224 | biostudies-literature

Self-assembled supramolecular nano vesicles for safe and highly efficient gene delivery to solid tumors.

Project description:The main obstacles for cationic polyplexes in gene delivery are in vivo instability and low solid-tumor accumulation. Safe vectors with high transfection efficiency and in vivo tumor accumulation are therefore highly desirable. In this study, the amphiphilic block copolymer poly(n-butyl methacrylate)-b-poly(N-acryloylmorpholine) was synthesized by reversible addition-fragmentation chain-transfer (RAFT) radical polymerization. The corresponding well-defined vesicles with narrow size distribution were tailored by finely regulating the packing parameter (?) of copolymer (1/2 < ? < 1). Compared with traditional "gold-standard" polycation (polyethylenimine, 25 kDa), plasmid DNA condensing efficiency, DNase I degradation protection, and cellular uptake were improved by the supramolecular nano vesicles. In addition, the plasmid DNA transferring efficiency in 10% fetal bovine serum medium was enlarged five times to that of polyethylenimine in renal tubular epithelial and human hepatocellular carcinoma cell lines. This improved in vitro transfection was mainly attributed to the densely packed bilayer. This stealth polyplex showed high serum stability via entropic repulsion, which further protected the polyplex from being destroyed during sterilization. As indicated by the IVIS(®) Lumina II Imaging System (Caliper Life Sciences, Hopkinton, MA) 24 hours post-intravenous administration, intra-tumor accumulation of the stealth polyplex was clearly promoted. This study successfully circumvented the traditional dilemma of efficient gene transfection at a high nitrogen-from-polyethylenimine to phosphate-from-DNA ratio that is accompanied with site cytotoxicity and low stability. As such, these simply tailored noncytotoxic nano vesicles show significant potential for use in practical gene therapy.

| S-EPMC3430442 | biostudies-literature

Solvent-Driven Supramolecular Wrapping of Self-Assembled Structures.

Project description:Self-assembly relies on the ability of smaller and discrete entities to spontaneously arrange into more organized systems by means of the structure-encoded information. Herein, we show that the design of the media can play a role even more important than the chemical design. The media not only determines the self-assembly pathway at a single-component level, but in a very narrow solvent composition, a supramolecular homo-aggregate can be non-covalently wrapped by a second component that possesses a different crystal lattice. Such a process has been followed in real time by confocal microscopy thanks to the different emission colors of the aggregates formed by two isolated PtII complexes. This coating is reversible and controlled by the media composition. Single-crystal X-ray diffraction and molecular simulations based on coarse-grained (CG) models allowed the understanding of the properties displayed by the different aggregates. Such findings could result in a new method to construct hierarchical supramolecular structures.

| S-EPMC7986396 | biostudies-literature

Supramolecular enzyme-mimicking catalysts self-assembled from peptides.

Project description:Natural enzymes catalyze biochemical transformations in superior catalytic efficiency and remarkable substrate specificity. The excellent catalytic repertoire of enzymes is attributed to the sophisticated chemical structures of their active sites, as a result of billions-of-years natural evolution. However, large-scale practical applications of natural enzymes are restricted due to their poor stability, difficulty in modification, and high costs of production. One viable solution is to fabricate supramolecular catalysts with enzyme-mimetic active sites. In this review, we introduce the principles and strategies of designing peptide-based artificial enzymes which display catalytic activities similar to those of natural enzymes, such as aldolases, laccases, peroxidases, and hydrolases (mainly the esterases and phosphatases). We also discuss some multifunctional enzyme-mimicking systems which are capable of catalyzing orthogonal or cascade reactions. We highlight the relationship between structures of enzyme-like active sites and the catalytic properties, as well as the significance of these studies from an evolutionary point of view.

| S-EPMC9830222 | biostudies-literature

Supramolecular Fractal Growth of Self-Assembled Fibrillar Networks.

Project description:Complex morphologies, as is the case in self-assembled fibrillar networks (SAFiNs) of 1,3:2,4-Dibenzylidene sorbitol (DBS), are often characterized by their Fractal dimension and not Euclidean. Self-similarity presents for DBS-polyethylene glycol (PEG) SAFiNs in the Cayley Tree branching pattern, similar box-counting fractal dimensions across length scales, and fractals derived from the Avrami model. Irrespective of the crystallization temperature, fractal values corresponded to limited diffusion aggregation and not ballistic particle-cluster aggregation. Additionally, the fractal dimension of the SAFiN was affected more by changes in solvent viscosity (e.g., PEG200 compared to PEG600) than crystallization temperature. Most surprising was the evidence of Cayley branching not only for the radial fibers within the spherulitic but also on the fiber surfaces.

| S-EPMC8167784 | biostudies-literature

Non-viral delivery of CRISPR/Cas9 complex using CRISPR-GPS nanocomplexes.

Project description:There is a critical need for the development of safe and efficient delivery technologies for CRISPR/Cas9 to advance translation of genome editing to the clinic. Non-viral methods that are simple, efficient, and completely based on biologically-derived materials could offer such potential. Here we report a simple and modular tandem peptide-based nanocomplex system with cell-targeting capacity that efficiently combines guide RNA (sgRNA) with Cas9 protein, and facilitates internalization of sgRNA/Cas9 ribonucleoprotein complexes to yield robust genome editing across multiple cell lines.

| S-EPMC7709491 | biostudies-literature

Self-assembled metal-phenolic nanocomplexes comprised of green tea catechin for tumor-specific ferroptosis.

Project description:Ferroptosis, a newly discovered form of regulated cell death, has garnered significant attention in the field of tumor therapy. However, the presence of overexpressed glutathione (GSH) and insufficient levels of H2O2 in the tumor microenvironment (TME) hinders the occurrence of ferroptosis. In response to these challenges, here we have constructed the self-assembled nanocomplexes (FeE NPs) utilizing epigallocatechin-3-gallate (EGCG) from green tea polyphenols and metal ions (Fe3+) as components. After grafting PEG, the nanocomplexes (FeE@PEG NPs) exhibit good biocompatibility and synergistically enhanced tumor-inhibitory properties. FeE@PEG NPs can be disassembled by H2O2 in the TME, leading to the rapid release of Fe3+ and EGCG. The released Fe3+ produces large amounts of toxic •OH by the Fenton reactions while having minimal impact on normal cells. The generated •OH effectively induces lipid peroxidation, which leads to ferroptosis in tumor cells. Meanwhile, the released EGCG can autoxidize to produce H2O2, which further promotes the production of •OH radicals and increases lipid peroxide levels. Moreover, EGCG also depletes the high levels of intracellular GSH, leading to an intracellular redox imbalance and triggering ferroptosis. This study provides new insights into advancing anticancer ferroptosis through rational material design, offering promising avenues for future research.

| S-EPMC10999486 | biostudies-literature

Self-Assembled Alkylated Polyamine Analogs as Supramolecular Anticancer Agents.

Project description:Conformationally restrained polyamine analog PG11047 is a well-known drug candidate that modulates polyamine metabolism and inhibits cancer cell growth in a broad spectrum of cancers. Here, we report a structure-activity relationship study of the PG11047 analogs (HPGs) containing alkyl chains of varying length, while keeping the unsaturated spermine backbone unchanged. Synthesis of higher symmetrical homologues was achieved through a synthetic route with fewer steps than the previous route to PG11047. The amphiphilic HPG analogs underwent self-assembly and formed spherically shaped nanoparticles whose size increased with the hydrophobic alkyl group's increasing chain length. Assessment of the in vitro anticancer activity showed more than an eight-fold increase in the cancer cell inhibition activity of the analogs with longer alkyl chains compared to PG11047 in human colon cancer cell line HCT116, and a more than ten-fold increase in human lung cancer cell line A549. Evaluation of the inhibition of spermine oxidase (SMOX) showed no activity for PG11047, but activity was observed for its higher symmetrical homologues. Comparison with a reference SMOX inhibitor MDL72527 showed nine-fold better activity for the best performing HPG analog.

| S-EPMC9032695 | 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