Quercetin Nanoparticles Research Articles

Quercetin conjugated with silica nanoparticles inhibits tumor growth in MCF-7 breast cancer cell lines

BackgroundQuercetin is a plant polyphenol from the flavonoid group that plays a fundamental role in controlling homeostasis due to its potent antioxidant properties. However, quercetin has extremely low water solubility, which is a major challenge in drug absorption. MethodIn this study, we described a simple method for the synthesis of quercetin nanoparticles. The quercetin nanoparticles had an average diameter of 82 nm and prominent yellow emission under UV irradiation. Therefore, we used an in vitro model treated with quercetin and quercetin nanoparticles to investigate the effects of quercetin nanoparticles on MCF-7 breast cancer cell line. FindingMCF-7 cells were cultured with different concentrations (1–100 μM) of quercetin nanoparticles at the 24th, 48th and 72 nd hours, and cell cycle and apoptosis assays were detected by flow cytometry (FCM). In this study, we found that quercetin nanoparticles (1–100 μM) could significantly reduce cell vitality, growth rate and colony formation of MCF-7 cells. ConclusionQuercetin nanoparticles can inhibit cell growth by blocking the cell cycle and promoting apoptosis in MCF-7 cells more than quercetin. As a result, quercetin nanoparticles may be useful therapy or prevention on breast cancer.

Cryoprotectant choice and analyses of freeze-drying drug suspension of nanoparticles with functional stabilisers

Freeze-drying is an effective way to improve long-term physical stability of nanosuspension in drug delivery applications. Nanosuspension also known as suspension of nanoparticles. In this study, the effect of freeze-drying with different cryoprotectants on the physicochemical characteristics of resveratrol (RSV) nanosuspension and quercetin (QUE) nanosuspension was evaluated. D-α-tocopheryl polyethylene glycol succinate (TPGS) and folate-modified distearoylphosphatidyl ethanolamine-polyethylene glycol (DSPE-PEG-FA) were selected as functional stabilisers formulated nanosuspension which were prepared by anti-solvent precipitation method. RSV nanoparticle size and QUE nanoparticle size were about 210 and 110 nm, respectively. The AFM and TEM results of nanosuspension showed uniform and irregular shape particles. After freeze-drying, the optimal concentration of four cryoprotectants was determined by the particle size of re-dispersed nanoparticles. The dissolution profile of drug nanoparticle significantly showed approximately at a 6–8-fold increase dissolution rate. Moreover, TPGS and DSPE-PEG-FA stabilised RSV nanosuspension and QUE nanosuspension samples showed better effect on long-term physical stability.

Quercetin nanoparticles with enhanced bioavailability as multifunctional agents toward amyloid induced neurotoxicity.

Quercetin (Que), as one of the most potent flavonoids, has gained appreciable attention in anti-fibrosis, anti-oxidation and other therapeutic research due to its numerous pharmacological and biological functions. However, low aqueous solubility, poor permeability and instability in physiological media have limited its widespread application in the pharmaceutical field. Herein, a facile method for fabrication of Que nanoparticles (NPs) has been developed by pulsed laser ablation (PLA). Que NPs exhibited homogeneous morphology with an average diameter of 50 nm and narrow distributions, which revealed enhanced solubility and drug release activity. Owing to the advance of NPs in modulating the amyloid fibrillation process as well as the anti-oxidative ability, Que NPs were applied to regulate Aβ42 assembly and they showed multifunctional effects: inhibiting Aβ aggregation, destabilizing Aβ fibrils, decreasing Aβ-induced oxidative stress and Aβ-mediated cytotoxicity. Thus, Que NPs with enhanced bioavailability may act as a multifunctional therapeutic agent toward amyloid-related diseases.

Quercetin nanoparticles alter pharmacokinetics of bromocriptine, reflecting its enhanced inhibitory action on liver and intestinal CYP 3A enzymes in rats

1. Quercetin is a dietary flavonoid has extremely low water solubility and found to possess CYP3A inhibitory activity. The purpose of the present study was to evaluate the effect of quercetin and quercetin nanoparticles (NQC) on the pharmacokinetics of bromocriptine (BRO) in rats.2. NQC prepared by antisolvent precipitation method and characterized by SEM and dissolution test. The following methods were used in this study i.e. in vitro liver and intestinal CYP3A microsomal activity and in vitro non-everted sac method. To confirm these findings, an in vivo pharmacokinetic study was also performed.3. The results indicate that quercetin significantly (p < 0.05) inhibited the CYP3A activity in liver and intestinal microsomes. In non-everted sac study, the intestinal transport and Papp of BRO were significantly increased in NQC and quercetin groups. Furthermore, in vivo study revealed that the increased levels of Cmax and AUC were comparatively high in NQC pretreated group than quercetin group. In addition, pretreatment with quercetin and NQC significantly (p < 0.05) decreased the mean CL/F and Vd/F of BRO.4. NQC pretreatment might be result in higher plasma levels of quercetin that could inhibit the CYP3A enzyme and enhanced the bioavailability of BRO.

Preparation, characterization and in vivo evaluation of pH sensitive, safe quercetin-succinylated chitosan-alginate core-shell-corona nanoparticle for diabetes treatment

The study aims for development of an efficient polymeric carrier for evaluating pharmaceutical potentialities in modulating the drug profile of quercetin (QUE) in anti-diabetic research. Alginate and succinyl chitosan are focused in this investigation for encapsulating quercetin into core-shell nanoparticles through ionic cross linking. The FT-IR, XRD, NMR, SEM, TEM, drug entrapment and loading efficiency are commenced to examine the efficacy of the prepared nanoparticles in successful quercetin delivery. Obtained results showed the minimum particle size of ∼91.58nm and ∼95% quercetin encapsulation efficiently of the particles with significant pH sensitivity. Kinetics of drug release suggested self-sustained QUE release following the non-fickian trend. A pronounced hypoglycaemic effect and efficient maintenance of glucose homeostasis was evident in diabetic rat after peroral delivery of these quercetin nanoparticles in comparison to free oral quercetin. This suggests the fabrication of an efficient carrier of oral quercetin for diabetes treatment.

Paclitaxel and quercetin nanoparticles co-loaded in microspheres to prolong retention time for pulmonary drug delivery.

High drug resistance, poor water solubility, short half-life, and low local drug concentration are obstacles for successful delivery of chemotherapeutic drugs for lung cancer. A new method involving the use of nanoparticles (NPs) for pulmonary delivery is proposed. However, use of NPs is limited by the particle size range for pulmonary drug delivery considering that NPs cannot be deposited directly into the lungs. NPs polymerized into microspheres (polymeric microspheres, PMs) will result in suitable particle sizes and retain the advantages of nanodrugs after redispersion when applied in pulmonary delivery. We report the development of novel NPs in the form of PMs loaded with paclitaxel (PTX) and quercetin (QUE) double drugs based on the synthesis of oleic acid-conjugated chitosan (OA-CTS) for pulmonary delivery. This approach is aimed toward prolonging PTX retention time in the presence of QUE and bypassing P-glycoprotein drug efflux pumps. NPs loaded with PTX or QUE were prepared with 11% substitution degree using OA-CTS as the carrier by ionic cross-linking method, which NPs loaded with PTX or QUE were used in the preparation of PMs by spray-drying. The diameters of the PMs ranged from 1 to 5 μm which had uniform size range. Scanning electron microscopy showed that PMs were polymers formed by a large number of NPs and readily redispersed (after redispersion, size of NPs ranged between 250 and 350 nm) in water within 1 h. PMs displayed slow-release characteristics at pH 4.5 and 7.4. The in vivo pharmacokinetic and biodistribution studies suggested that PMs exhibit prolonged circulation time and a markedly high accumulation in the lung. The obtained results indicate that PMs can serve as a promising pulmonary delivery system for combined pharmacotherapy using hydrophobic anticancer drugs.

Quercetin nanoparticle complex attenuated diabetic nephropathy via regulating the expression level of ICAM-1 on endothelium.

The purpose of the study was to reveal the therapeutic effect of quercetin (QUE) nanoparticle complex on diabetic nephropathy (DN) by regulating the expression of intercellular adhesion molecular-1 (ICAM-1) on endothelium as compared to free QUE. QUE 10 mg/kg as a single abdominal subcutaneous injection daily for 8 weeks continuously in diabetic rats and 10 mg/kg QUE nanoparticle complex as a single abdominal subcutaneous injection every 5 days, continuously administered for 8 weeks to diabetic rats. Blood and left kidneys were collected; pathological change of kidney, renal function, oxidative stress level, blood glucose level, serum lipid, urine protein, and albumin/creatinine ratio were measured; and neutrophil adhesion, ICAM-1 expression, and CD11b+ cells infiltration were observed. Both QUE and QUE nanoparticle complex preconditioning ameliorated the pathological damage of kidney and improved renal function, alleviated renal oxidative stress injury, restricted inflammatory cells infiltration, and downregulated the ICAM-1 expression as compared to DN group, while QUE nanoparticle complex significantly alleviated this effect.

English

Diabetes is directly involved in oxidative stress production. Therefore, this study was conducted to investigate the morphological and functional alterations caused by oxidative stress and to evaluate the antioxidant effect of quercetin nanoparticles (QUNPs) in streptozotocin (STZ)-induced diabetic (type II) rats. Seventy two male albino adult rats were randomly distributed in 6 different experimental groups, with 12 animals per group: Normal Control (NC) group, Positive Control (PC) group received one dose of STZ (60 mg/kg body weight [bw]); QUNPs 10 mg/kg bw/day alone group; QUNPs 10 mg/kg bw/day + one dose of STZ (60 mg/kg bw) group; QUNPs 20 mg/kg bw/day alone group; and QUNPs 20 mg/kg bw/day + one dose of STZ (60 mg/kg bw) group. STZ-diabetic rats were treated with QUNPs (10 and 20 mg/kg bw/day) for 7 weeks to analyze their effects on markers of renal enzymes antioxidant [malondialdehyde (MDA), catalase (CAT), glutathione reductase (GR), and glutathione peroxidase (GPx)], total protein and albumin, and also on kidney tissues. The results showed that the particle size of QUNPs is 16.13 nm at flow rate 10 ml/min. QUNPs especially at the dosage of 20 mg/kg bw/day gave results close to normal values observed in NC compared to PC. Also, histopathology of kidney sections for QUNPs 20 mg/kg bw/day + STZ and QUNPs (10 and 20 mg/kg bw/day) alone, appeared similar to NC. It can be concluded that QUNPs could become a promising adjuvant in the treatment of diabetes mellitus and can act as an antioxidant agent. Key words: Diabetic, streptozotocin, free radical, antioxidant.

Improving quercetin dissolution and bioaccessibility with reduced crystallite sizes through media milling technique

Quercetin (QC) is a common bioflavonoid with low water solubility, which limits its oral bioavailability and in vivo beneficial functions. To enhance QC bioaccessibility, QC nanoparticles were produced using the media milling technology. Hydrophobically modified starch (HMS) was added with the ratio of 1:1 to QC as a stabilizer to prevent the agglomeration of QC particles. The QC nanodispersions were either spray-dried or freeze-dried after media milling process. Physicochemical characteristics of dried QC powders were measured through dynamic light scattering (DLS), Fourier Transform-Infrared spectroscopy (FTIR), dissolution test and X-ray diffraction (XRD). The detailed crystallite structures were carefully analyzed. The TNO dynamic gastro-intestinal model-1 (TIM-1) was utilized to study the in vitro QC bioaccessibility by simulation of the digestive processes in the upper GI tract. This study suggests that media milling technique combined with spray/freeze-drying treatment is an efficient processing method for the development of crystalline nutraceuticals-based functional food products with reduced crystallite sizes and enhanced metastable equilibrium solubility, dissolution and bioaccessibility.

Quercetin Remodels the Tumor Microenvironment To Improve the Permeation, Retention, and Antitumor Effects of Nanoparticles.

Our previous work demonstrated that Wnt16 expression in cisplatin-damaged tumor-associated fibroblasts is a key factor contributing to cisplatin resistance in malignancies. Natural antifibrotic compounds with low toxicities are promising candidates to downregulate Wnt16 expression, improving the antitumor effect of cisplatin nanoparticles. Upon screening several natural chemicals, we found that a dietary flavonoid, quercetin, significantly suppresses Wnt16 expression in activated fibroblasts. To facilitate drug delivery, we have prepared a targeted lipid/calcium/phosphate nanoparticle formulation consisting of a prodrug of quercetin, i.e., quercetin phosphate, with a high loading efficiency (26.6% w/w). This quercetin nanoparticle with a particle size of around 35 nm significantly improved the bioavailability and metabolic stability of the parent quercetin. Quercetin phosphate is released from the nanoparticles and converted back to the parent quercetin under physiological conditions. Following systemic administration of quercetin phosphate nanoparticles, a significant downregulation in Wnt16 expression was observed and further yielded a synergistic antitumor effect with cisplatin nanoparticles in a stroma-rich bladder carcinoma model. The α-SMA-positive fibroblast and collagen within the tumor decreased significantly after combination treatment. This suggests that the remodeling of the tumor microenvironment induced by quercetin plays a critical role in promoting the synergy. Indeed, our data further confirmed that quercetin phosphate alone significantly remodeled the tumor microenvironment and increased the penetration of second-wave nanoparticles into the tumor nests. Collectively, quercetin phosphate nanoparticles may be a safe and effective way to improve therapeutic treatment for desmoplastic tumors.

Hepatoprotective and free radical scavenging actions of quercetin nanoparticles on aflatoxin B1-induced liver damage: in vitro/in vivo studies

The objective of present study was in vitro and in vivo evaluation of hepatoprotective and antioxidant activity of Quercetin nanoparticles (Q NPs) against toxicity induced by aflatoxin B1. The Q NPs were prepared using precipitation method. Hepatocytes were prepared by the method of collagenase enzyme perfusion via portal vein. The NPs were characterized in terms of size and morphology using dynamic light scattering (DLS) and transmission electron microscopy (TEM), respectively. The level of parameters, such as cell death, ROS formation, lipid peroxidation, mitochondrial membrane potential and cellular glutathione (GSH) content, in the aflatoxin B1-treated and non-treated hepatocytes were determined and the mentioned markers were assessed in the presence of Q NPs. The prepared NPs showed particle size of 52.70 nm with polydispersity index (PDI) of 0.18. In contrast to free Q, the administration of Q NPs more efficiently decreased the rate of ROS formation, lipid peroxidation and improved cell viability, mitochondrial membrane potential and glutathione level and showed a significant hepatoprotective efiect by reducing levels of aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase. It is suggested that the Q NPs is a promising candidate for drug delivery, which enhances the hepatoprotective effect of Q against the cytotoxic effects of aflatoxin B1.

Transcriptome Analysis Reveals Silver Nanoparticle-Decorated Quercetin Antibacterial Molecular Mechanism.

Facile and simple method is developed to synthesize silver-nanoparticle-decorated quercetin nanoparticles (QA NPs). Modification suggests that synergistic quercetin (Qe) improves the antibacterial effect of silver nanoparticles (Ag NPs). Characterization experiment indicates that QA NPs have a diameter of approximately 10 nm. QA NPs show highly effective antibacterial activities against drug-resistant Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). We explore antibacterial mechanisms using S. aureus and E. coli treated with QA NPs. Through morphological changes in E. coli and S. aureus, mechanisms are examined for bacterial damage caused by particulate matter from local dissociation of silver ion and Qe from QA NPs trapped inside membranes. Moreover, we note that gene expression profiling methods, such as RNA sequencing, can be used to predict discover mechanisms of toxicity of QA NPs. Gene ontology (GO) assay analyses demonstrate the molecular mechanism of the antibacterial effect of QA NPs. Regarding cellular component ontology, "cell wall organization or biogenesis" (GO: 0071554) and "cell wall macromolecule metabolic process" (GO: 0044036) are the most represented categories. The present study reports that transcriptome analysis of the mechanism offers novel insights into the molecular mechanism of antibacterial assays.

Quercetin nanoparticles display antitumor activity via proliferation inhibition and apoptosis induction in liver cancer cells.

Quercetin is a potent cancer therapeutic agent and dietary antioxidant present in fruit and vegetables. Quercetin prevents tumor proliferation by inducing cell cycle arrest and is a well known cancer therapeutic agent and autophagy mediator. Recent studies showed that drug delivery by nanoparticles have enhanced efficacy with reduced side effects. In this regard, gold-quercetin into poly(DL-lactide-co-glycolide) nanoparticles was examined. In this study, we explored the role and possible underlying mechanisms of quercetin nanoparticle in regulation of antitumor activity in liver cancer cells. Treatment with quercetin nanoparticle effectively inhibited the liver cancer cell proliferation, cell migration and colony formation, thus suppressing liver cancer progression. Quercetin nanoparticle also upregulated apoptosis markedly. Further study suggested that quercetin nanoparticle accelerated the cleavage of caspase-9, caspase-3, and induced the up-releasing of cytochrome c (Cyto-c), contributing to apoptosis in liver cancer cells. Quercetin nanoparticles also promoted telomerase reverse transcriptase (hTERT) inhibition through reducing AP-2β expression and decreasing its binding to hTERT promoter. In addition, quercetin nanoparticle had an inhibitory role in cyclooxygenase 2 (COX-2) via suppressing the NF-κB nuclear translocation and its binding to COX-2 promoter. Quercetin nanoparticle also inactivated Akt and ERK1/2 signaling pathway. Taken together, our results suggested that quercetin nanoparticle had an antitumor effect by inactivating caspase/Cyto-c pathway, suppressing AP-2β/hTERT, inhibiting NF-κB/COX-2 and impeding Akt/ERK1/2 signaling pathways. Our results provided new mechanistic basis for further investigation of quercetin nanoparticles to find potential therapeutic strategies and possible targets for liver cancer inhibition.

Preparation, characterization, and enhanced antimicrobial activity: quercetin-loaded PLGA nanoparticles against foodborne pathogens

The use of quercetin as a bioflavonoid is becoming increasingly common in food industries even though poor water solubility, instability, absorption, and permeability have limited its application. The oil-in-water single-emulsion solvent evaporation method to synthesize highly stable and soluble quercetin-encapsulated nanoparticles (NPs), in which the reaction yield, particle size, and polydispersity of the NPs are varied greatly within the process parameters of the synthesis method, has been optimized. NPs with different initial quercetin amounts were used to determine how the quercetin amount affected nanoparticle properties and antimicrobial eficiency. Listeria monocytogenes, Salmonella typhimurium, Escherichia coli, and Staphylococcus aureus were chosen as model bacteria due to their being foodborne pathogens. The results of antimicrobial activity evaluated by three different methods showed that the antimicrobial activity of both quercetin NPs and free quercetin was effective on gram-positive strains (L. monocytogenes and S. aureus). Additionally, it was detected that Q31 NPs have more effective antimicrobial activity than other synthesized quercetin nanoparticles depending on the amount of substance and release. Furthermore, on the basis of assessing the antibacterial effects by scanning electron microscopy, it was detected that bacteria cells lost their integrity and became pale with the release of cytoplasm and decomposed after treatment with Q31 NPs.

Synergistic Effect of Quercetin Nanoparticles on Liver and Pancreas Tissues and Oxidative Stress of Streptozotocin-Induced Diabetic Rats

Synergistic Effect of Quercetin Nanoparticles on Liver and Pancreas Tissues and Oxidative Stress of Streptozotocin-Induced Diabetic Rats

Enhancement of oral bioavailability of rivastigmine with quercetin nanoparticles by inhibiting CYP3A4 and esterases.

Quercetin is a well-known flavonoid, has pharmacokinetic interaction with ester drugs due to its capability of esterase inhibition in the gut and liver. However, the interaction between quercetin nanoparticles (NQC) and rivastigmine has not been reported. Hence, the present study was performed to evaluate the effect of quercetin alone and its nanoparticles on the pharmacokinetics of rivastigmine in rats. NQC prepared by antisolvent precipitation method. The influence of quercetin on the pharmacokinetics of rivastigmine was evaluated by following methods i.e. in vitro inhibitory effect on esterase enzyme in rat liver microsomes and in vitro assessment of CYP3A activity using erythromycin-N-demethylase (EMD) assay. To confirm these findings, an in vivo pharmacokinetic study of orally administered rivastigmine in rats with quercetin and NQC pretreatments was performed. The size of NQC was observed below 300nm. Quercetin significantly (p<0.05) inhibited the esterase-mediated metabolism of rivastigmine. In in vitro assessment of CYP3A activity model the erythromycin-N-demethylation (EMD) levels in quercetin treated group were significantly reduced (p<0.05). Cmax, AUC0-t and AUC0- ∞ of rivastigmine were found to be increased in quercetin and NQC pretreated groups. Further, the CL/F and Vd/F of rivastigmine were significantly decreased. The results revealed that enhanced bioavailability of rivastigmine might be caused by the combination of their effects due to CYP3A and esterase inhibition, Therefore, concomitant administration of NQC influences the bioavailability of rivastigmine and also has synergetic effect in the treatment of Alzheimer's disease.

Quercetin nanoparticles attenuates scopolamine induced spatial memory deficits and pathological damages in rats

Quercetin is a well-known flavonoid, has low bioavailability. Quercetin nanoparticles (NQC) enhance its bioavailability. NQC were not explored for their potential therapeutic activities in Alzheimer’s disease (AD). Hence, the present study was performed to evaluate the protective effect of NQC in comparison to free quercetin against scopolamine induced spatial memory impairments.NQC prepared by anti solvent precipitation method. Quercetin, NQC (30mg/kg p.o.) and rivastigmine (2mg/kg i.p.) as a reference drug were administered for 8 consecutive days. At the end of the treatment period memory impairments were induced by a single injection of scopolamine (20mg/kg; i.p.). Conditioned avoidance and rectangular-maze tests were conducted 30min thereafter then rats were sacrificed and brain homogenates were used for the estimation of glutathione (GSH), catalase and malondialdehyde (MDA) contents together with acetyl cholinesterase (AchE) activity. In addition, histopathologic studies were also performed.The size of NQC was observed below 300nm. NQC significantly reduced the transfer latency and conditioned avoidance response compared to scopolamine treated group (p<0.05). Pretreatment with NQC showed a significant (p<0.05) decrease in MDA, AchE levels and increase in brain catalase and GSH levels to be similar to that observed in the rivastigmine group.In all the behavioral, biochemical and histological experiments, the rats treated with NQC showed additional distinguished results compared to quercetin group indicating that a preventive strategy against the progression of AD. This approach of quercetin nanoparticles provides the potential therapeutic application in human neurodegenerative disease in future.

Quercetin nanoparticles induced autophagy and apoptosis through AKT/ERK/Caspase-3 signaling pathway in human neuroglioma cells: In vitro and in vivo.

Neuroglioma is a complex neuroglial tumor involving dysregulation of many biological pathways at multiple levels. Quercetin is a potent cancer therapeutic agent presented in fruit and vegetables, preventing tumor proliferation, and is a well known cancer therapeutic agent and autophagy mediator. Recent studies showed that drug delivery by nanoparticles have enhanced efficacy with reduced side effects. In this regard, gold-quercetin into poly (dl-lactide-co-glycolide) nanoparticles was examined. In the present study, quercetin nanoparticle induced cell autophagy and apoptosis in human neuroglioma cell was investigated. Quercetin nanoparticle administrated to animals displayed suppressed role in tumor growth. The cell viability was deterined through CCK8 assay. Transmission electron microscopy was utilized to observe the formation of autophagosome. The cell apoptosis was assessed by annexin V-PI staining. The protein expression of cell autophagy regulators and tumor suppressors were analyzed via western blot and RT-PCR. Treatment of human neuroglioma cell with quercetin nanoparticle induced cell death in a dose-and time-dependent manner. The flow cytometry results showed that the proportion of the apoptosis cells had gained after quercetin nanoparticle treatment compared to untreatment group. Moreover, the expression of activated PI3K/AKT and Bcl-2 were down-regulated upon quercetin nanoparticle treatment in human neuroglioma cells. The expression level of LC3 and ERK as well as cytoplasm p53, cleaved Caspase-3 and PARP was positively correlated with the concentration of quercetin nanoparticle. In addition, p-mTOR and GAIP were obviously down-regulated by quercetin nanoparticle treatment in a dose-dependent manner. These results indicated that quercetin nanoparticle could induce autophagy and apoptosis in human neuroglioma cells, the underlying molecular mechanisms, at least partly, through activation LC3/ERK/Caspase-3 and suppression AKT/mTOR signaling.

Design of PLGA-functionalized quercetin nanoparticles for potential use in Alzheimer’s disease

Dysfunctional interaction of amyloid-β (Aβ) with excess metal ions is proved to be related to the etiology of Alzheimer’s disease (AD). Hence, disruption of these metal-peptide interactions using nanoparticles (NPs) holds considerable promise as a therapeutic strategy to combat this incurable disease. Given that quercetin is a natural product, the biocompatibility and small size essential for permeating the blood-brain barrier make it a potential therapeutic drug candidate for treating AD. Nanocarriers formulated with the US Food and Drug Administration-approved biocompatible and biodegradable polymer PLGA are being widely explored for the controlled delivery of therapeutic drugs, proteins, peptides, oligonucleotides, and genes. With this background, the present study was undertaken to investigate the effects of PLGA-functionalized quercetin (PLGA@QT) NPs on inhibited and disassembled Aβ42 fibrils and the PLGA@QT NPs have low cytotoxicity when tested on SH-SY5Y cells in vitro. As expected, the cytotoxicity studies of the PLGA@QT NPs led to a concentration-related behaviour on the SH-SY5Y human neuroblastoma cells. And, it has demonstrated that PLGA@QT NPs can inhibit the neurotoxicity of Zn2+-Aβ42 system and enhance the viability of neuron cells. The results from behavioral tests indicate that injection of PLGA@QT NPs into APP/PS1 mice ameliorate cognition and memory impairments. Most encouragingly, the in vivo systemic toxicity of PLGA@QT NPs examined by histological analysis in major organs did not show any signs of adverse effect to mice. Thus, the prepared quercetin based nanoscale drug delivery carrier efficiently enhanced the therapeutic index and reduced the side effects. Our findings are highly encouraging, providing substantial evidence of the safety of PLGA@QT NPs for biomedical application. We expect these findings will be relevant for other NPs for treatment of AD and have broad implications in NP-based studies and applications.

The effect of quercetin nanoparticle on cervical cancer progression by inducing apoptosis, autophagy and anti-proliferation via JAK2 suppression.

Cervical cancer is a cause of cancer death, making it as the one of the most common cause for death among women globally. Though many studies before have explored a lot for cervical cancer prevention and treatment, there are still a lot far from to know based on the molecular mechanisms. Janus kinase 2 (JAK2) has been reported to play an essential role in the progression of apoptosis, autophagy and proliferation for cells. We loaded gold-quercetin into poly (dl-lactide-co-glycolide) nanoparticles to cervical cancer cells due to the propertities of quercetin in ameliorating cellular processes and the easier absorbance of nanoparticles. Here, in our study, quercetin nanoparticles (NQ) were administrated to cells to investigate the underlying mechanism by which the cervical cancer was regulated. First, JAK2-inhibited carvical cancer cell lines were involved for our experiments in vitro and in vivo. Western blotting, quantitative RT-PCR (qRT-PCR), ELISA, Immunohistochemistry, and flow-cytometric analysis were used to determine the key signaling pathway regulated by JAK2 for cervical cancer progression. And the role of quercetin nanoparticles was determined during the process. Data here indicated that JAK2, indeed, expressed highly in cancer cell lines compared to the normal cervical cells. And apoptosis and autophagy were found in JAK2-inhibited cancer cells through activating Caspase-3, and suppressing Cyclin-D1 and mTOR regulated by Signal Transducer and Activator of Transcription (STAT) 3/5 and phosphatidylinositide 3-kinase/protein kinases (PI3K/AKT) signaling pathway. The cervical cancer cells proliferation was inhibited. Further, tumor size and weight were reduced by inhibition of JAK2 in vivo experiments. Notably, administration with quercetin nanoparticles displayed similar role with JAK2 suppression, which could inhibit cervical cancer cells proliferation, invasion and migration. In addition, autophogy and apoptosis were induced, promoting cervical cancer cell death. To our knowledge, it was the first time to evaluate the role of quercetin nanoparticles in improving cervical cancer from apoptosis, autophagy and proliferation, which could be a potential target for future therapeutic approach clinically.