Browse
Submit Data
Databases
API
Help

Dataset Information

14 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Neuroprotective Effect of siRNA Entrapped in Hyaluronic Acid-Coated Lipoplexes by Intravitreal Administration.

ABSTRACT: Since the possibility of silencing specific genes linked to retinal degeneration has become a reality with the use of small interfering RNAs (siRNAs), this technology has been widely studied to promote the treatment of several ocular diseases. Despite recent advances, the clinical success of gene silencing in the retina is significantly reduced by inherent anatomical and physiological ocular barriers, and new strategies are required to achieve intraocular therapeutic effectiveness. In this study, we developed lipoplexes, prepared with sodium alginate as an adjuvant and strategically coated with hyaluronic acid (HA-LIP), and investigated the potential neuroprotective effect of these systems in a retinal light damage model. Successful functionalization of the lipoplexes with hyaluronic acid was indicated in the dynamic light scattering and transmission electron microscopy results. Moreover, these HA-LIP nanoparticles were able to protect and deliver siRNA molecules targeting caspase-3 into the retina. After retinal degeneration induced by high light exposure, in vitro and in vivo quantitative reverse transcription-PCR (RT-qPCR) assays demonstrated significant inhibition of caspase-3 expression by HA-LIP. Furthermore, these systems were shown to be safe, as no evidence of retinal toxicity was observed by electroretinography, clinical evaluation or histology.

SUBMITTER: Ribeiro MCS

PROVIDER: S-EPMC8226864 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Cellular responses of hyaluronic acid-coated chitosan nanoparticles.

Project description:In recent years, nanotechnology has been proven to offer promising biomedical applications for in vivo diagnostics and drug delivery, stressing the importance of thoroughly investigating the biocompatibility of potentially translatable nanoparticles (NPs). Herein, we report the cellular responses of uncoated chitosan NPs (CS NPs) and hyaluronic acid-coated chitosan NPs (HA-CS NPs) when introduced into Chinese hamster ovary cells (CHO-K1) in a dose-dependent manner (2.5, 0.25, 0.025, 0.0025, and 0.00025 mg mL-1) at two time points (24 and 48 h). MTS assay, cell proliferation, showed a decrease in the viability of cells when treated with 0.25 and 2.5 mg mL-1 CS NPs. When exposed to high doses of CS NPs, the lactate dehydrogenase (LDH) enzyme started to leak out of the cells and the cellular levels of mitochondrial potentials were significantly reduced accompanied by a high production of intracellular reactive oxygen species (ROS). Our study provides molecular evidence of the biocompatibility offered by HA-CS NPs, through ROS scavenging capabilities rescuing cells from the oxidative stress, showing no observed cellular stress and thereby revealing the promising effect of anionic hyaluronic acid to significantly reduce the cytotoxicity of CS NPs. Our findings are important to accelerate the translation and utilization of HA-CS NPs in drug delivery, demonstrating the pronounced effect of surface modifications on modulating the biological responses.

| S-EPMC6116812 | biostudies-other

Co-Injection of Sulfotyrosine Facilitates Retinal Uptake of Hyaluronic Acid Nanospheres Following Intravitreal Injection.

Project description:Gene and drug delivery to the retina is a critical therapeutic goal. While the majority of inherited forms of retinal degeneration affect the outer retina, specifically the photoreceptors and retinal pigment epithelium, effective targeted delivery to this region requires invasive subretinal delivery. Our goal in this work was to evaluate two innovative approaches for increasing both the persistence of delivered nanospheres and their penetration into the outer retina while using the much less invasive intravitreal delivery method. We formulated novel hyaluronic acid nanospheres (HA-NS, 250 nm and 500 nm in diameter) conjugated to fluorescent reporters and delivered them intravitreally to the adult Balb/C mouse retina. They exhibited persistence in the vitreous and along the inner limiting membrane (ILM) for up to 30 days (longest timepoint examined) but little retinal penetration. We thus evaluated the ability of the small molecule, sulfotyrosine, to disrupt the ILM, and found that 3.2 µg/µL sulfotyrosine led to significant improvement in delivery to the outer retina following intravitreal injections without causing retinal inflammation, degeneration, or loss of function. Co-delivery of sulfotyrosine and HA-NS led to robust improvements in penetration of HA-NS into the retina and accumulation along the interface between the photoreceptors and the retinal pigment epithelium. These exciting findings suggest that sulfotyrosine and HA-NS may be an effective strategy for outer retinal targeting after intravitreal injection.

| S-EPMC8469555 | biostudies-literature

Hyaluronic Acid Coated Acid-Sensitive Nanoparticles for Targeted Therapy of Adjuvant-Induced Arthritis in Rats.

Project description:Activated macrophages play a vital role in rheumatoid arthritis (RA) pathophysiology. CD44 is an overexpressed receptor on activated macrophages that is a potential target site for RA treatment. In this study, we prepared hyaluronic acid (HA) coated acid-sensitive polymeric nanoparticles (HAPNPs) composed of egg phosphatidylcholine, polyethylenimine, and poly (cyclohexane-1,4-diyl acetone dimethylene ketal) (PCADK) loaded with dexamethasone (Dex) for the treatment of RA. PCADK was used to form polymeric cores because of its acid-sensitivity. The HAPNPs were about 150 nm in size and had a zeta potential of -2.84 mV. The release rate of Dex from HAPNPs/Dex in vitro increased markedly when the pH decreased from 7.4 to 4.5, indicating that the HAPNPs were pH-sensitive. In a cellular uptake study, stronger fluorescence signals were observed in activated macrophages treated with HAPNPs, suggesting that HAPNPs could be effective nanodevices target to activated macrophages. In rats with adjuvant-induced arthritis, HAPNPs could inhibited the progression of RA. Taken together, these results suggest that the HAPNPs could be useful in RA therapy.

| S-EPMC6337373 | biostudies-literature

siRNA-loaded selenium nanoparticle modified with hyaluronic acid for enhanced hepatocellular carcinoma therapy.

Project description:BackgroundSmall interfering RNA (siRNA) as a new therapeutic modality holds promise for cancer treatment. However, the traditional viral carriers are prone to immunogenicity and risk of insertional mutagenesis.MethodsIn order to provide a tumor-targeted delivery carrier of siRNA in cancer therapy, the hyaluronic acid (HA)-selenium (Se)-polyethylenimine (PEI) nanoparticle (NP) was fabricated by decorating SeNP with HA as a tumor-targeting moiety and by linking the polycationic polymers polyethylenimine PEI onto the surface of SeNP. The siRNA was loaded to the surface of SeNP HA-Se-PEI via the electrostatic interaction between siRNA and PEI to prepare the functionalized SeNP HA-Se-PEI@siRNA.ResultsThe HA-Se-PEI@siRNA was internalized into the HepG2 cell mainly in a clathrin-mediated endocytosis manner. Owing to the active tumor-targeted effect mediated by HA, HA-Se-PEI@siRNA achieved the obvious higher transfection efficiency, greater gene silencing ability, and stronger cytotoxicity in the HepG2 cell compared with the passive tumor-targeted NP Se-PEI@siRNA. The knockdown of hairy and enhancer of split 5 by HA-Se-PEI@siRNA induced the HepG2 cell cycle arrest at the G0/G1 phase and apoptosis. Furthermore, the treatment with HA-Se-PEI@siRNA resulted in greater antitumor efficacy compared with the Se-PEI@siRNA in vitro and in vivo. In addition, the HA-Se-PEI@siRNA was almost no toxic to the key organs of mice.ConclusionThese findings provided an alternative therapeutic route for targeted cancer treatments.

| S-EPMC5858822 | biostudies-literature

Hyaluronic Acid Coated Chitosan Nanoparticles Reduced the Immunogenicity of the Formed Protein Corona.

Project description:Studying the interactions of nanoparticles (NPs) with serum proteins is necessary for the rational development of nanocarriers. Optimum surface chemistry is a key consideration to modulate the formation of the serum protein corona (PC) and the resultant immune response. We investigated the constituent of the PC formed by hyaluronic acid-coated chitosan NPs (HA-CS NPs). Non-decorated chitosan NPs (CS NPs) and alginate-coated chitosan NPs (Alg-CS NPs) were utilized as controls. Results show that HA surface modifications significantly reduced protein adsorption relative to controls. Gene Ontology analysis demonstrates that HA-CS NPs were the least immunogenic nanocarriers. Indeed, less inflammatory proteins were adsorbed onto HA-CS NPs as opposed to CS and Alg-CS NPs. Interestingly, HA-CS NPs differentially adsorbed two unique anti-inflammatory proteins (ITIH4 and AGP), which were absent from the PC of both controls. On the other hand, CS and Alg-CS NPs selectively adsorbed a proinflammatory protein (Clusterin) that was not found on the surfaces of HA-CS NPs. While further studies are needed to investigate abilities of the PCs of only ITIH4 and AGP to modulate the interaction of NPs with the host immune system, our results suggest that this proof-of-concept could potentially be utilized to reduce the immunogenicity of a wide range of nanomaterials.

| S-EPMC5585335 | biostudies-literature

Effect of hyaluronic acid incorporation method on the stability and biological properties of polyurethane-hyaluronic acid biomaterials.

Project description:The high failure rate of small diameter vascular grafts continues to drive the development of new materials and modification strategies that address this clinical problem, with biomolecule incorporation typically achieved via surface-based modification of various biomaterials. In this work, we examined whether the method of biomolecule incorporation (i.e., bulk versus surface modification) into a polyurethane (PU) polymer impacted biomaterial performance in the context of vascular applications. Specifically, hyaluronic acid (HA) was incorporated into a poly(ether urethane) via bulk copolymerization or covalent surface tethering, and the resulting PU-HA materials characterized with respect to both physical and biological properties. Modification of PU with HA by either surface or bulk methods yielded materials that, when tested under static conditions, possessed no significant differences in their ability to resist protein adsorption, platelet adhesion, and bacterial adhesion, while supporting endothelial cell culture. However, only bulk-modified PU-HA materials were able to fully retain these characteristics following material exposure to flow, demonstrating a superior ability to retain the incorporated HA and minimize enzymatic degradation, protein adsorption, platelet adhesion, and bacterial adhesion. Thus, despite bulk methods rarely being implemented in the context of biomolecule attachment, these results demonstrate improved performance of PU-HA upon bulk, rather than surface, incorporation of HA. Although explored only in the context of PU-HA, the findings revealed by these experiments have broader implications for the design and evaluation of vascular graft modification strategies.

| S-EPMC3945677 | biostudies-literature

The development and evaluation of hyaluronic acid coated mitochondrial targeting liposomes for celastrol delivery.

Project description:In order to precisely deliver celastrol into mitochondria of tumor cells, improve antitumor efficacy of celastrol and overcome its troublesome problems in clinical application, a novel multistage-targeted celastrol delivery system (C-TL/HA) was developed via electrostatic binding of hyaluronic acid (HA) to celastrol-loaded cationic liposomes composed of natural soybean phosphatidylcholine and cholesterol modified with mitochondrial targeting molecular TPP. Study results in this article showed that C-TL/HA successfully transported celastrol into mitochondria, effectively activated apoptosis of mitochondrial pathway, exerted higher tumor inhibition efficiency and lower toxic side effects compared with free celastrol. More importantly, HA coating not only enabled this delivery system to have good stability and safety in vivo, but also increased drug uptake and facilitated tumor targeting through recognizing CD44 receptors rich on the surface of tumor cells. Conclusively, this HA-coated mitochondrial targeting liposomes may provide a prospect for the clinical application of celastrol in tumor therapy.

| S-EPMC9828745 | biostudies-literature

Effect of using amino acids in the freeze-drying of siRNA lipoplexes on gene knockdown in cells after reverse transfection.

Project description:Recently, small interfering RNA (siRNA)/cationic liposome complexes (siRNA lipoplexes) have become a crucial research tool for studying gene function. Easy and reliable siRNA transfection with a large set of siRNAs is required for the successful screening of gene function. Reverse (Rev)-transfection with freeze-dried siRNA lipoplexes is validated for siRNA transfection with a large set of siRNAs in a multi-well plate. In our previous study, it was shown that Rev-transfection with siRNA lipoplexes freeze-dried in disaccharides or trisaccharides resulted in long-term stability with a high level of gene-knockdown activity. In the present study, the effects of amino acids used as cryoprotectants in the freeze-drying of siRNA lipoplexes on gene knockdown via Rev-transfection were assessed. A total of 15 types of amino acids were used to prepare freeze-dried siRNA lipoplexes, and it was found that the freeze-drying of siRNA lipoplexes with amino acid concentrations >100 mM strongly suppressed targeted gene expression regardless of the amino acid type; however, some amino acids strongly upregulated or downregulated gene expression in the cells transfected with negative control siRNA. Amongst the amino acids tested, the presence of asparagine showed specific gene-knockdown activity, forming large cakes after freeze-drying and retaining a favorable siRNA lipoplex size after rehydration. These findings provide valuable information regarding amino acids as cryoprotectants for Rev-transfection using freeze-dried siRNA lipoplexes for the efficient delivery of siRNA into cells.

| S-EPMC8329998 | biostudies-literature

Hyaluronic acid-modified manganese-chelated dendrimer-entrapped gold nanoparticles for the targeted CT/MR dual-mode imaging of hepatocellular carcinoma.

Project description:Hepatocellular carcinoma (HCC) is the most common malignant tumor of the liver. The early and effective diagnosis has always been desired. Herein, we present the preparation and characterization of hyaluronic acid (HA)-modified, multifunctional nanoparticles (NPs) targeting CD44 receptor-expressing cancer cells for computed tomography (CT)/magnetic resonance (MR) dual-mode imaging. We first modified amine-terminated generation 5 poly(amidoamine) dendrimers (G5.NH2) with an Mn chelator, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), fluorescein isothiocyanate (FI), and HA. Then, gold nanoparticles (AuNPs) were entrapped within the above raw product, denoted as G5.NH2-FI-DOTA-HA. The designed multifunctional NPs were formed after further Mn chelation and purification and were denoted as {(Au0)100G5.NH2-FI-DOTA(Mn)-HA}. These NPs were characterized via several different techniques. We found that the {(Au0)100G5.NH2-FI-DOTA(Mn)-HA} NPs exhibited good water dispersibility, stability under different conditions, and cytocompatibility within a given concentration range. Because both AuNPs and Mn were present in the product, {(Au0)100G5.NH2-FI-DOTA(Mn)-HA} displayed a high X-ray attenuation intensity and favorable r1 relaxivity, which are advantageous properties for targeted CT/MR dual-mode imaging. This approach was used to image HCC cells in vitro and orthotopically transplanted HCC tumors in a unique in vivo model through the CD44 receptor-mediated endocytosis pathway. This work introduces a novel strategy for preparing multifunctional NPs via dendrimer nanotechnology.

| S-EPMC5032118 | biostudies-literature

Hyaluronic acid based self-assembling nanosystems for CD44 target mediated siRNA delivery to solid tumors.

Project description:Anticancer therapeutics employing RNA interference mechanism holds promising potentials for sequence-specific silencing of target genes. However targeted delivery of siRNAs to tumor tissues and cells and more importantly, their intracellular release at sites of interest still remains a major challenge that needs to be addressed before this technique could become a clinically viable option. In the current study, we have engineered and screened a series of CD44 targeting hyaluronic acid (HA) based self-assembling nanosystems for targeted siRNA delivery. The HA polymer was functionalized with lipids of varying carbon chain lengths/nitrogen content, as well as polyamines for assessing siRNA encapsulation. From the screens, several HA-derivatives were identified that could stably encapsulate/complex siRNAs and form self-assembled nanosystems, as determined by gel retardation assays and dynamic light scattering. Many HA derivatives could transfect siRNAs into cancer cells overexpressing CD44 receptors. Interestingly, blocking the CD44 receptors on the cells using free excess soluble HA prior to incubation of cy3-labeled-siRNA loaded HA nano-assemblies resulted in >90% inhibition of the receptor mediated uptake, confirming target specificity. In addition, SSB/PLK1 siRNA encapsulated in HA-PEI/PEG nanosystems demonstrated dose dependent and target specific gene knockdown in both sensitive and resistant A549 lung cancer cells overexpressing CD44 receptors. More importantly, these siRNA encapsulated nanosystems demonstrated tumor selective uptake and target specific gene knock down in vivo in solid tumors as well as in metastatic tumors. The HA based nanosystems thus portend to be promising siRNA delivery vectors for systemic targeting of CD44 overexpressing cancers including tumor initiating (stem-) cells and metastatic lesions.

| S-EPMC3636539 | 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