Electrophysiological effects of polyethylene glycol modified gold nanoparticles on mouse hippocampal neurons
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ABSTRACT:
SUBMITTER: Tuna B
PROVIDER: S-EPMC7779771 | biostudies-literature | 2020 Dec
REPOSITORIES: biostudies-literature
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Project description:We report a new use of dendrimer-entrapped gold nanoparticles (Au DENPs) modified by polyethylene glycol (PEG) with good biocompatibility for in vitro and in vivo imaging of atherosclerotic mice by computed tomography (CT). In this study, Au DENPs were synthesized using poly(amidoamine) (PAMAM) dendrimers of generation 5 (G5.NH2) modified by PEG monomethyl ether (G5.NH2-mPEG20) as templates. In vitro cytotoxicity and flow cytometry assays show that the formed PEGylated Au DENPs have good biocompatibility and are non-cytotoxic at the Au concentration up to 300 μM. Silver staining and transmission electron microscopy (TEM) further confirm that the Au DENPs are able to be uptaken by macrophages and are located dominantly in the lysosomes of the cells. Importantly, the formed PEGylated Au DENPs are able to be used for CT imaging of murine macrophages in vitro and macrophages in atherosclerotic mice in vivo using apolipoprotein-E-gene-deficient mice as a model. These findings suggest that the formed PEGylated Au DENPs are a promising contrast agent for CT imaging of atherosclerosis.
| S-EPMC4184899 | biostudies-literature
Project description:A gold nanoparticle (AuNP)-based colorimetric method was developed for the molecular weight (MW) determination of polyethylene glycol (PEG), a commonly used hydrophilic polymer. Addition of a salt solution to PEG-coated AuNP solutions helps in screening the electrostatic repulsion between nanoparticles and generating a color change of the solutions from wine red to blue in 10 min in accordance with the MW of PEG, which illustrates the different stability degrees (SDs) of the AuNPs. The SDs are calculated by the absorbance ratios of the stable to the aggregated AuNPs in the solution. The root mean square end-to-end length (〈h2〉1/2) of PEG molecules shows a linear fit to the SDs of the PEG-coated AuNPs in a range of 1.938 ± 0.156 to 10.151 ± 0.176 nm. According to the Derjaguin-Landau-Verwey-Overbeek theory, the reason for this linear relationship is that the thickness of the PEG adlayer is roughly equivalent to the 〈h2〉1/2 of the PEG molecules in solution, which determines the SDs of the AuNPs. Subsequently, the MW of the PEG can be obtained from its 〈h2〉1/2 using a mathematical relationship between 〈h2〉1/2 and MW of PEG molecule. Applying this approach, we determined the 〈h2〉1/2 and the MW of four PEG samples according to their absorbance values from the ordinary ultraviolet-visible spectrophotometric measurements. Therefore, the MW of PEG can be distinguished straightforwardly by visual inspection and determined by spectrophotometry. This novel approach is simple, rapid, and sensitive.
| S-EPMC3878192 | biostudies-literature
Project description:Purpose: Novel collagenase IV (ColIV) and clusterin (CLU)-modified polycaprolactone-polyethylene glycol (PCL-PEG) nanoparticles that load doxorubicin (DOX) were designed and fully evaluated in vitro and in vivo. Methods: PCL-PEG-ColIV was synthesized by linking PCL-PEG and ColIV through a carbodiimide method. DOX-loaded nanoparticles (DOX-PCL-PEG-ColIV) were self-assembly prepared, followed by noncovalently adsorbing CLU on the DOX-PCL-PEG-ColIV surface to obtain DOX-PCL-PEG-ColIV /CLU nanoparticles, which can penetrate through the tumor extracellular matrix (ECM) and inhibit phagocytosis by macrophage. The physicochemical properties of nanoparticles were characterized. The cellular uptake and antiphagocytosis ability of nanoparticles in MCF-7 tumor cells and RAW264.7 cells were investigated. The penetration ability of nanoparticles was individually evaluated in the two-dimensional (2D) and three-dimensional (3D) ECM models. The tissue distribution and antitumor effect of nanoparticles were evaluated in MCF-7 cell-bearing nude mice. Results: Compared with DOX-PCL-PEG-COOH nanoparticles, DOX-PCL-PEG-ColIV/CLU nanoparticles could effectively overcome the phagocytosis by RAW264.7 and showed excellent cellular uptake in MCF-7 cells. In addition, they showed remarkable penetration ability through the 2D and 3D ECM models. DOX-PCL-PEG-ColIV/CLU nanoparticles significantly reduced the drug distribution in the liver and spleen and enhanced the drug accumulation in tumor tissue compared with DOX-PCL-PEG-COOH or DOX-PCL-PEG-ColIV nanoparticles. DOX-PCL-PEG-ColIV/CLU nanoparticles showed remarkable antitumor effect but did not cause severe pathological damages in the main tissues, including the heart, liver, spleen, lung, and kidney. Conclusion: Novel ColIV and CLU-modified PCL-PEG nanoparticles showed excellent cellular uptake, ECM penetration, antiphagocytosis, and antitumor effects both in vitro and in vivo.
| S-EPMC7738847 | biostudies-literature
Project description:Failure of the mammalian central nervous system (CNS) to regenerate effectively after injury leads to mostly irreversible functional impairment. Gold nanoparticles (AuNPs) are promising candidates for drug delivery in combination with tissue-compatible reagents, such as polyethylene glycol (PEG). PEG administration in CNS injury models has received interest for potential therapy, but toxicity and low bioavailability prevents clinical application. Here we show that intraspinal delivery of PEG-functionalized 40-nm-AuNPs at early stages after mouse spinal cord injury is beneficial for recovery. Positive outcome of hind limb motor function was accompanied by attenuated inflammatory response, enhanced motor neuron survival, and increased myelination of spared or regrown/sprouted axons. No adverse effects, such as body weight loss, ill health, or increased mortality were observed. We propose that PEG-AuNPs represent a favorable drug-delivery platform with therapeutic potential that could be further enhanced if PEG-AuNPs are used as carriers of regeneration-promoting molecules.
| S-EPMC4817765 | biostudies-literature
Project description:Emphasis using phototheranostics has been placed on the construction of multifunctional nanoplatforms for simultaneous tumor diagnosis and therapy. Herein, we put forth a novel nanosized luminescent material using the incorporation of red emissive carbon dots on gold nanorods through polyethylene glycol as a covalent linkage for dual-modal imaging and photothermal therapy. The novel nanohybrids, not only retain the optical properties of the gold nanorod and carbon dots, but also possess superior imaging performance in both confocal laser scanning microscopy and fluorescence lifetime imaging microscopy. The nanohybrids also exhibit excellent photothermal performance as phototheranostic nanohybrid probes for in vitro assays. This study promises a new multifunctional nanoplatform for cancer diagnostics and therapeutics.
| S-EPMC6165167 | biostudies-literature
Project description:The aim of this study is to investigate the protective effect of polyethylene glycol capped gold nanoparticles (PEG-AuNPs) on renal ischemia-reperfusion injury (I/R)-induced acute kidney injury (AKI) in diabetic mice via the activation of adenosine 5' monophosphate-activated protein kinase-nuclear factor erythroid-2-related factor-2 (AMPK-Nrf2) pathway. Diabetes was induced in male mice (12/group) by streptozotocin (50 mg/kg) for 5 consecutive days. After 4 weeks, the mice have intravenously received doses of PEG-AuNPs (40, 150, and 400 µg/kg body weight) for 3 consecutive days, and then animals were subjected to 30 min ischemia and 48 h reperfusion. Following the treatment with three different doses of PEG-AuNPs, the levels of blood urea nitrogen (BUN) and creatinine were reduced. Obvious reduction in renal tubular atrophy, glomerular damage, mitochondrial damage, and necrotic area were ultra-structurally detected, and renal interstitial inflammation and apoptosis were diminished. Moreover, PEG-AuNPs increased the recovering of damaged renal cells, suppressed significantly levels of malondialdehyde (MDA), downregulated significantly the level of inflammatory cytokines (TNF-α and IL-1β), and upregulated the AMPK-Nrf2 pathway. PEG-AuNPs exhibited a promising alternative therapeutic target for diabetic renal I/R-induced AKI through upregulation of AMPK/PI3K/AKT path which additionally stimulated Nrf2-regulated antioxidant enzymes in a dose-dependent manner.
| S-EPMC9581836 | biostudies-literature
Project description:ObjectiveGold nanoparticles have attracted enormous interest as potential theranostic agents. However, little is known about the long-term elimination and systemic toxicity of gold nanoparticles in the literature. Hollow gold nanospheres (HAuNS) is a class of photothermal conducting agent that have shown promises in photoacoustic imaging, photothermal ablation therapy, and drug delivery. It's very necessary to make clear the biosafety of HAuNS for its further application.MethodsWe investigated the cytotoxicity, complement activation, and platelet aggregation of polyethylene glycol (PEG)-coated HAuNS (PEG-HAuNS, average diameter of 63 nm) in vitro and their pharmacokinetics, biodistribution, organ elimination, hematology, clinical chemistry, acute toxicity, and chronic toxicity in mice.ResultsPEG-HAuNS did not induce detectable activation of the complement system and did not induce detectable platelet aggregation. The blood half-life of PEG-HAuNS in mice was 8.19?±?1.4 hr. The single effective dose of PEG-HAuNS in photothermal ablation therapy was determined to be 12.5 mg/kg. PEG-HAuNS caused no adverse effects after 10 daily intravenous injections over a 2-week period at a dose of 12.5 mg/kg per injection (accumulated dose: 125 mg/kg). Quantitative analysis of the muscle, liver, spleen, and kidney revealed that the levels of Au decreased 45.2%, 28.6%, 41.7%, and 40.8%, respectively, from day 14 to day 90 after the first intravenous injection, indicating that PEG-HAuNS was slowly cleared from these organs in mice.ConclusionOur data support the use of PEG-HAuNS as a promising photothermal conducting agent.
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Project description:Zoledronic acid (ZOL) has been approved as the only bisphosphonate for the prevention and treatment of metastatic bone diseases with acceptable safety and tolerability. However, systemic or direct injection of ZOL often causes severe side effects, which limits its clinical application. Here, an innovative nano-drug delivery system, ZOL-loaded hyaluronic acid/polyethylene glycol/nano-hydroxyapatite nanoparticles (HA-PEG-nHA-ZOL NPs), has been found to effectively inhibit the proliferation of three types of human osteosarcoma cell lines (143b, HOS, and MG63) at 1-10 μmol/L, while with low cell cytotoxicity on normal cells. The NPs significantly enhanced the apoptosis-related protein expression and tumor cell apoptosis rate. The NPs could also inhibit the proliferation of osteosarcoma cells by blocking the S phase of the cell cycle. In the orthotopic osteosarcoma nude mice model, local injection of the HA-PEG-nHA-ZOL NPs stimulated tumor necrosis, apoptosis, and granulocyte infiltration in the blood vessels. Altogether, the ZOL nano-delivery system possesses great potential for local treatment to prevent local tumor recurrence and can be applied in clinical osteosarcoma therapy.
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Project description:n-butylidenephthalide (BP) has been verified as having the superior characteristic of cancer cell toxicity. Furthermore, gold (Au) nanoparticles are biocompatible materials, as well as effective carriers for delivering bio-active molecules for cancer therapeutics. In the present research, Au nanoparticles were first conjugated with polyethylene glycol (PEG), and then cross-linked with BP to obtain PEG-Au-BP nanodrugs. The physicochemical properties were characterized through ultraviolet-visible spectroscopy (UV-Vis), Fourier-transform infrared spectroscopy (FTIR), and dynamic light scattering (DLS) to confirm the combination of PEG, Au, and BP. In addition, both the size and structure of Au nanoparticles were observed through scanning electron microscopy (SEM) and transmission electron microscopy (TEM), where the size of Au corresponded to the results of DLS assay. Through in vitro assessments, non-transformed BAEC and DBTRG human glioma cells were treated with PEG-Au-BP drugs to investigate the tumor-cell selective cytotoxicity, cell uptake efficiency, and mechanism of endocytic routes. According to the results of MTT assay, PEG-Au-BP was able to significantly inhibit DBTRG brain cancer cell proliferation. Additionally, cell uptake efficiency and potential cellular transportation in both BAEC and DBTRG cell lines were observed to be significantly higher at 2 and 24 h. Moreover, the mechanisms of endocytosis, clathrin-mediated endocytosis, and cell autophagy were explored and determined to be favorable routes for BAEC and DBTRG cells to absorb PEG-Au-BP nanodrugs. Next, the cell progression and apoptosis of DBTRG cells after PEG-Au-BP treatment was investigated by flow cytometry. The results show that PEG-Au-BP could remarkably regulate the DBTRG cell cycle at the Sub-G1 phase, as well as induce more apoptotic cells. The expression of apoptotic-related proteins in DBTRG cells was determined through Western blotting assay. After treatment with PEG-Au-BP, the apoptotic cascade proteins p21, Bax, and Act-caspase-3 were all significantly expressed in DBTRG brain cancer cells. Through in vivo assessments, the tissue morphology and particle distribution in a mouse model were examined after a retro-orbital sinus injection containing PEG-Au-BP nanodrugs. The results demonstrate tissue integrity in the brain (forebrain, cerebellum, and midbrain), heart, liver, spleen, lung, and kidney, as they did not show significant destruction due to PEG-Au-BP treatment. Simultaneously, the extended retention period for PEG-Au-BP nanodrugs was discovered, particularly in brain tissue. The above findings identify PEG-Au-BP as a potential nanodrug for brain cancer therapies.
| S-EPMC9325228 | biostudies-literature
Project description:Although the potent anti-parkinsonian action of the atypical D?-like receptor agonist SKF83959 has been attributed to the selective activation of phosphoinositol(PI)-linked D? receptor, whereas the mechanism underlying its potent neuroprotective effect is not fully understood. In the present study, the actions of SKF83959 on neuronal membrane potential and neuronal excitability were investigated in CA1 pyramidal neurons of rat hippocampal slices. SKF83959 (10-100 µM) caused a concentration-dependent depolarization, associated with a reduction of input resistance in CA1 pyramidal neurons. The depolarization was blocked neither by antagonists for D?, D?, 5-HT(2A/2C) receptors and ??-adrenoceptor, nor by intracellular dialysis of GDP-?-S. However, the specific HCN channel blocker ZD7288 (10 µM) antagonized both the depolarization and reduction of input resistance caused by SKF83959. In voltage-clamp experiments, SKF83959 (10-100 µM) caused a concentration-dependent increase of Ih current in CA1 pyramidal neurons, which was independent of D? receptor activation. Moreover, SKF83959 (50 µM) caused a 6 mV positive shift in the activation curve of Ih and significantly accelerated the activation of Ih current. In addition, SKF83959 also reduced the neuronal excitability of CA1 pyramidal neurons, which was manifested by the decrease in the number and amplitude of action potentials evoked by depolarizing currents, and by the increase of firing threshold and rhoebase current. The above results suggest that SKF83959 increased Ih current through a D? receptor-independent mechanism, which led to the depolarization of hippocampal CA1 pyramidal neurons. These findings provide a novel mechanism for the drug's neuroprotective effects, which may contributes to its therapeutic benefits in Parkinson's disease.
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