Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Nanogels with Selective Intracellular Reactivity for Intracellular Tracking and Delivery.

ABSTRACT: A multimodal approach for hydrogel-based nanoparticles was developed to selectively allow molecular conjugated species to either be released inside the cell or remain connected to the polymer network. Using the intrinsic difference in reactivity between esters and amides, nanogels with an amide-conjugated dye could be tracked intracellularly localizing next to the nucleus, while ester-conjugation allowed for liberation of the molecular species from the hydrogel network inside the cell, enabling delivery throughout the cytoplasm. The release was a result of particle exposure to the intracellular environment. The conjugation approach and polymer network building rely on the same chemistry and provide a diverse range of possibilities to be used in nanomedicine and theranostic approaches.

SUBMITTER: Zu G

PROVIDER: S-EPMC7756612 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Nanogels with Selective Intracellular Reactivity for Intracellular Tracking and Delivery.

Zu Guangyue G Mergel Olga O Ribovski Laís L Bron Reinier R Zuhorn Inge S IS van Rijn Patrick P

Chemistry (Weinheim an der Bergstrasse, Germany) 20201019 66

A multimodal approach for hydrogel-based nanoparticles was developed to selectively allow molecular conjugated species to either be released inside the cell or remain connected to the polymer network. Using the intrinsic difference in reactivity between esters and amides, nanogels with an amide-conjugated dye could be tracked intracellularly localizing next to the nucleus, while ester-conjugation allowed for liberation of the molecular species from the hydrogel network inside the cell, enabling ...[more]

PMID: 32608127

Similar Datasets

Attoliter protein nanogels from droplet nanofluidics for intracellular delivery.

Project description:Microscale hydrogels consisting of macromolecular networks in aqueous continuous phases have received increasing attention because of their potential use in tissue engineering, cell encapsulation and for the storage and release of cargo molecules. However, for applications targeting intracellular delivery, their micrometer-scale size is unsuitable for effective cellular uptake. Nanoscale analogs of such materials are thus required for this key area. Here, we describe a microfluidics/nanofluidics-based strategy for generating monodisperse nanosized water-in-oil emulsions with controllable sizes ranging from 2500 ± 110 nm down to 51 ± 6 nm. We demonstrate that these nanoemulsions can act as templates to form protein nanogels stabilized by supramolecular fibrils from three different proteins. We further show that these nanoparticles have the ability to penetrate mammalian cell membranes and deliver intracellular cargo. Due to their biocompatibility and lack of toxicity, natural protein-based nanoparticles present advantageous characteristics as vehicles for cargo molecules in the context of pharmaceutical and biomedical applications.

| S-EPMC7007244 | biostudies-literature

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

Uptake and function of membrane-destabilizing cationic nanogels for intracellular drug delivery.

Project description:The design of intracellular drug delivery vehicles demands an in-depth understanding of their internalization and function upon entering the cell to tailor the physicochemical characteristics of these platforms and achieve efficacious treatments. Polymeric cationic systems have been broadly accepted to be membrane disruptive thus being beneficial for drug delivery inside the cell. However, if excessive destabilization takes place, it can lead to adverse effects. One of the strategies used to modulate the cationic charge is the incorporation of hydrophobic moieties, thus increasing the hydrophobic content. We have demonstrated the successful synthesis of nanogels based on diethylaminoethyl methacrylate and poly(ethylene glycol) methyl ether methacrylate. Addition of the hydrophobic monomers tert-butyl methacrylate or 2-(tert-butylamino)ethyl methacrylate shows improved polymer hydrophobicity and modulation of the critical swelling pH. Here, we evaluate the cytocompatibility, uptake, and function of these membrane-destabilizing cationic methacrylated nanogels using in vitro models. The obtained results suggest that the incorporation of hydrophobic monomers decreases the cytotoxicity of the nanogels to epithelial colorectal adenocarcinoma cells. Furthermore, analysis of the internalization pathways of these vehicles using inhibitors and imaging flow cytometry showed a significant decrease in uptake when macropinocytosis/phagocytosis inhibitors were present. The membrane-disruptive abilities of the cationic polymeric nanogels were confirmed using three different models. They demonstrated to cause hemolysis in sheep erythrocytes, lactate dehydrogenase leakage from a model cell line, and disrupt giant unilamellar vesicles. These findings provide new insights of the potential of polymeric nanoformulations for intracellular delivery.

| S-EPMC6336667 | biostudies-literature

Coating and Functionalization Strategies for Nanogels and Nanoparticles for Selective Drug Delivery.

Project description:Drug delivery is a fascinating research field with several development opportunities. Great attention is now focused on colloidal systems, nanoparticles, and nanogels and on the possibility of modifying them in order to obtain precise targeted drug delivery systems. The aim of this review is to give an overview of the main available surface functionalization and coating strategies that can be adopted in order to modify the selectivity of the nanoparticles in the delivery process and obtain a final system with great targeted drug delivery ability. We also highlight the most important fields of application of these kinds of delivery systems and we propose a comparison between the advantages and disadvantages of the described functionalization strategies.

| S-EPMC7151136 | biostudies-literature

A Size-Selective Intracellular Delivery Platform.

Project description:Identifying and separating a subpopulation of cells from a heterogeneous mixture are essential elements of biological research. Current approaches require detailed knowledge of unique cell surface properties of the target cell population. A method is described that exploits size differences of cells to facilitate selective intracellular delivery using a high throughput microfluidic device. Cells traversing a constriction within this device undergo a transient disruption of the cell membrane that allows for cytoplasmic delivery of cargo. Unique constriction widths allow for optimization of delivery to cells of different sizes. For example, a 4 μm wide constriction is effective for delivery of cargo to primary human T-cells that have an average diameter of 6.7 μm. In contrast, a 6 or 7 μm wide constriction is best for large pancreatic cancer cell lines BxPc3 (10.8 μm) and PANC-1 (12.3 μm). These small differences in cell diameter are sufficient to allow for selective delivery of cargo to pancreatic cancer cells within a heterogeneous mixture containing T-cells. The application of this approach is demonstrated by selectively delivering dextran-conjugated fluorophores to circulating tumor cells in patient blood allowing for their subsequent isolation and genomic characterization.

| S-EPMC5337179 | biostudies-literature

Magnetic Force-driven in Situ Selective Intracellular Delivery.

Project description:Intracellular delivery of functional materials holds great promise in biologic research and therapeutic applications but poses challenges to existing techniques, including the reliance on exogenous vectors and lack of selectivity. To address these problems, we propose a vector-free approach that utilizes millimeter-sized iron rods or spheres driven by magnetic forces to selectively deform targeted cells, which in turn generates transient disruption in cell membranes and enables the delivery of foreign materials into cytosols. A range of functional materials with the size from a few nanometers to hundreds of nanometers have been successfully delivered into various types of mammalian cells in situ with high efficiency and viability and minimal undesired effects. Mechanistically, material delivery is mediated by force-induced transient membrane disruption and restoration, which depend on actin cytoskeleton and calcium signaling. When used for siRNA delivery, CXCR4 is effectively silenced and cell migration and proliferation are significantly inhibited. Remarkably, cell patterns with various complexities are generated, demonstrating the unique ability of our approach in selectively delivering materials into targeted cells in situ. In summary, we have developed a magnetic force-driven intracellular delivery method with in situ selectivity, which may have tremendous applications in biology and medicine.

| S-EPMC6155070 | biostudies-literature

Preparation of Biodegradable Oligo(lactide)s-Grafted Dextran Nanogels for Efficient Drug Delivery by Controlling Intracellular Traffic.

Project description:Nanogels, nanometer-sized hydrogel particles, have great potential as drug delivery carriers. To achieve effective drug delivery to the active sites in a cell, control of intracellular traffic is important. In this study, we prepared nanogels composed of dextran with oligolactide (OLA) chains attached via disulfide bonds (Dex-g-SS-OLA) that collapse under the reductive conditions of the cytosol to achieve efficient drug delivery. In addition, we introduced galactose (Gal) residues on the nanogels, to enhance cellular uptake by receptor-mediated endocytosis, and secondary oligo-amine (tetraethylenepentamine) groups, to aid in escape from endosomes via proton sponge effects. The obtained Dex-g-SS-OLA with attached Gal residues and tetraethylenepentamine (EI₄) groups, EI₄/Gal-Dex-g-SS-OLA, formed a nanogel with a hydrodynamic diameter of ca. 203 nm in phosphate-buffered solution. The collapse of the EI₄/Gal-Dex-g-SS-OLA nanogels under reductive conditions was confirmed by a decrease in the hydrodynamic diameter in the presence of reductive agents. The specific uptake of the hydrogels into HepG2 cells and their intercellular behavior were investigated by flow cytometry and confocal laser scanning microscopy using fluorescence dye-labeled nanogels. Escape from the endosome and subsequent collapse in the cytosol of the EI₄/Gal-Dex-g-SS-OLA were observed. These biodegradable nanogels that collapse under reductive conditions in the cytosol should have great potential as efficient drug carriers in, for example, cancer chemotherapy.

| S-EPMC6032273 | biostudies-literature

Intracellular tracking of single-plasmid DNA particles after delivery by electroporation.

Project description:Electroporation is a physical method of transferring molecules into cells and tissues. It takes advantage of the transient permeabilization of the cell membrane induced by electric field pulses, which gives hydrophilic molecules access to the cytoplasm. This method offers high transfer efficiency for small molecules that freely diffuse through electrically permeabilized membranes. Larger molecules, such as plasmid DNA, face several barriers (plasma membrane, cytoplasmic crowding, and nuclear envelope), which reduce transfection efficiency and engender a complex mechanism of transfer. Our work provides insight into the way electrotransferred DNA crosses the cytoplasm to reach the nucleus. For this purpose, single-particle tracking experiments of fluorescently labeled DNA were performed. Investigations were focused on the involvement of the cytoskeleton using drugs disrupting or stabilizing actin and tubulin filaments as the two relevant cellular networks for particle transport. The analysis of 315 movies (~4,000 trajectories) reveals that DNA is actively transported through the cytoskeleton. The large number of events allows a statistical quantification of the DNA motion kinetics inside the cell. Disruption of both filament types reduces occurrence and velocities of active transport and displacements of DNA particles. Interestingly, stabilization of both networks does not enhance DNA transport.

| S-EPMC3863794 | biostudies-other

Peptide-functionalized nanogels for targeted siRNA delivery.

Project description:A major bottleneck in the development of siRNA therapies is their delivery to the desired cell type or tissue, followed by effective passage across the cell membrane with subsequent silencing of the targeted mRNA. To address this problem, we describe the synthesis of core/shell hydrogel nanoparticles (nanogels) with surface-localized peptides that specifically target ovarian carcinoma cell lines possessing high expression levels of the Eph2A receptor. These nanogels are also demonstrated to be highly effective in the noncovalent encapsulation of siRNA and enable cell-specific delivery of the oligonucleotides in serum-containing medium. Cell toxicity and viability assays reveal that the nanogel construct is nontoxic under the conditions studied, as no toxicity or decrease in cell proliferation is observed following delivery. Importantly, a preliminary investigation of gene silencing illustrates that nanogel-mediated delivery of siRNA targeted to the EGF receptor results in knockdown of that receptor. Excellent protection of siRNA during endosomal uptake and endosomal escape of the nanogels is suggested by these results since siRNA activity in the cytosol is required for gene silencing.

| S-EPMC2765502 | biostudies-literature

Internalized compartments encapsulated nanogels for targeted drug delivery.

Project description:Drug delivery systems inspired by natural particulates hold great promise for targeted cancer therapy. An endosome formed by internalization of plasma membrane has a massive amount of membrane proteins and receptors on the surface, which is able to specifically target the homotypic cells. Herein, we describe a simple method to fabricate an internalized compartments encapsulated nanogel with endosome membrane components (EM-NG) from source cancer cells. Following intracellular uptake of methacrylated hyaluronic acid (m-HA) adsorbed SiO2/Fe3O4 nanoparticles encapsulating a crosslinker and a photoinitiator, EM-NG was readily prepared through in situ crosslinking initiated under UV irradiation after internalization. The resulting nanogels loaded with doxorubicin (DOX) displayed enhanced internalization efficiency to the source cells through a specific homotypic affinity in vitro. However, when treated with the non-source cells, the EM-NGs exhibited insignificant difference in therapeutic efficiency compared to a bare HA nanogel with DOX. This study illustrates the potential of utilizing an internalized compartments encapsulated formulation for targeted cancer therapy, and offers guidelines for developing a natural particulate-inspired drug delivery system.

| S-EPMC5001168 | 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