Isoquercetin Ameliorates Osteoarthritis via Nrf2/NF-κB Axis: An In Vitro and In Vivo Study.

Osteoarthritis (OA) is a progressive joint disease characterized by extracellular matrix (ECM) degradation and inflammation, which is involved with pathological microenvironmental alterations induced by damaged chondrocytes. However, current therapies are not effective in alleviating the progression of OA. Isoquercetin is a natural flavonoid glycoside compound that has various pharmacological effects including anticancer, anti-diabetes and blood lipid regulation. Previous evidence suggests that isoquercetin has anti-inflammatory properties in various diseases, but its effect on OA has not been investigated yet. In this study, through western bolt, qRT-PCR and ELISA, it was found that isoquercetin could reduce the increase of ADAMTS5, MMP13, COX-2, iNOS and IL-6 induced by IL-1ß, suggesting that isoquercetin could inhibit the inflammation and ECM degradation of chondrocytes. Through nuclear-plasma separation technique, western blot and immunocytochemistry, it can be found that Nrf2 and NF-κB pathways are activated in this process, and isoquercetin may rely on this process to play its protective role. In vivo, the results of X-ray and SO staining show that intra-articular injection of isoquercetin reduces the degradation of cartilage in the mouse OA model. In conclusion, the present work suggests that isoquercetin may benefit chondrocytes by regulating the Nrf2/NF-κB signaling axis, which supports isoquercetin as a potential drug for the treatment of OA.

An electrochemical sensor based on porous heterojunction hollow NiCo-LDH/Ti3C2Tx MXenes composites for the detection of quercetin in natural plants.

Cubic hollow-structured NiCo-LDH was synthesized using a solvothermal method. Subsequently, clay-like Ti3C2Tx MXenes were electrostatically self-assembled with NiCo layered double hydroxides (NiCo-LDH) to form composites featuring three-dimensional porous heterostructures. The composites were characterized using SEM, TEM, XRD, XPS, and FT-IR spectroscopy. Ti3C2Tx MXenes exhibit excellent electrical conductivity and hydrophilicity, providing abundant binding sites for NiCo-LDH, thereby promoting an increase in ion diffusion channels. The formation of three-dimensional porous heterostructural composites enhances charge transport, significantly improving sensor sensitivity and response speed. Consequently, the sensor demonstrates excellent electrochemical detection capability for quercetin (Qu), with a detection range of 0.1-20 µM and a detection limit of 23 nM. Additionally, it has been applied to the detection of Qu in natural plants such as onion, golden cypress, and chrysanthemum. The recovery ranged from 97.6 to 102.28%.

The influence mechanism of pH and polyphenol structures on the formation, structure, and digestibility of pea starch-polyphenol complexes via high-pressure homogenization.

The formation of starch-polyphenol complexes through high-pressure homogenization (HPH) is a promising method to reduce starch digestibility and control postprandial glycemic responses. This study investigated the combined effect of pH (5, 7, 9) and polyphenol structures (gallic acid, ferulic acid, quercetin, and tannic acid) on the formation, muti-scale structure, physicochemical properties, and digestibility of pea starch (PS)-polyphenol complexes prepared by HPH. Results revealed that reducing pH from 9 to 5 significantly strengthened the non-covalent binding between polyphenols and PS, achieving a maximum complex index of 13.89 %. This led to the formation of complexes with higher crystallinity and denser structures, promoting a robust network post-gelatinization with superior viscoelastic and thermal properties. These complexes showed increased resistance to enzymatic digestion, with the content of resistant starch increasing from 28.66 % to 42.00 %, rapidly digestible starch decreasing from 42.82 % to 21.88 %, and slowly digestible starch reducing from 71.34 % to 58.00 %. Gallic acid formed the strongest hydrogen bonds with PS, especially at pH 5, leading to the highest enzymatic resistance in PS-gallic acid complexes, with the content of resistant starch of 42.00 %, rapidly digestible starch of 23.35 % and slowly digestible starch of 58.00 %, and starch digestion rates at two digestive stages of 1.82 × 10-2 min-1 and 0.34 × 10-2 min-1. These insights advance our understanding of starch-polyphenol interactions and support the development of functional food products to improve metabolic health by mitigating rapid glucose release.

Mannoproteins modulate olfactrory perception and copigmentation of organoleptic-active-components in wines: Effects and potential molecular mechanisms.

In this research, accelerated aroma release experiments and malvidin-3-O-glucoside copigmentation experiments in model red wine solutions were designed to investigate the abilities and molecular mechanisms of mannoproteins in modulating olfactory/chromatic properties of red wines. Results indicate that under orthonasal condition, mannoprotein MP2 was promising aroma modulator due to its predictable behaviors in expelling and retaining the aroma compounds during different periods. Low field nuclear magnetic resonance and molecular dynamic simulation proved that the modulation ability of MP2 should be explained by its transitionary interacting preferences with water/aroma compound molecules. Retronasal results show that the release of aroma compounds and olfactory perceptions were irregular and difficult to predict, probably due to the complexity of the retronasal condition. All mannoproteins protected malvidin-3-O-glucoside and quercetin via the formation of binary/ternary complexes, and quercetin was found prior to be protected than malvidin-3-O-glucoside. Principal mannoprotein A0A6C1DV26 might be the critical malvidin-3-O-glucoside protector. With the presence of quercetin, principal mannoproteins B3LQU1/B5VL26 in mannoprotein MP1 might exhibit intramolecular and/or intermolecular mechanisms that strengthened the hyperchromic effect, thus enhanced the copigmentation.

Development and characterization of polysiloxane-based gel loaded with phytoingredients encapsulated in phytosomes for scar management.

Recent research has emphasized the development of efficient drug delivery systems to facilitate the delivery of biological compounds such as polyphenols via skin absorption. Phytozomes have been employed as carriers of plant compounds in this context Hydrogen bonding between plant polyphenols and the phospholipid phosphate group enables efficient encapsulation of potent compounds for enhanced drug delivery systems. Additionally, the strong affinity of phytosomes for the skin's phospholipids enhances skin absorption. In this study, phytosomes were initially formulated using the thin-layer hydration method After optimizing the synthetic parameters, phytosomes were loaded with Resveratrol and Quercetin for enhanced delivery and skin absorption potential to assess the characteristics of the synthesized phytosomes, tests were conducted to determine particle distribution and size, zeta potential, and examine the microstructure morphology using a scanning electron microscope (SEM). Furthermore, a siloxane gel base was formulated in this study, and the stability of the physicochemical and biological properties of the final prepared nanoformulation was investigated. The results of this study indicated that the formulated phytosomes exhibit optimal characteristics for facilitating high skin penetration of resveratrol and quercetin. A high skin absorption was observed after 60 days of synthesis. Additionally, the base of the siloxane gel can play a significant role in preventing the formation of scars by reducing the passage of water vapor.

Anti- COVID-19 drug discovery by flavonoid derivatives: an extensive computational drug design approach.

The present study deals with the in-silico analyses of several flavonoid derivatives to explore COVID-19 through pharmacophore modelling, molecular docking, molecular dynamics, drug-likeness, and ADME properties. The initial literature study revealed that many flavonoids, including luteolin, quercetin, kaempferol, and baicalin may be useful against SARS ß-coronaviruses, prompting the selection of their potential derivatives to investigate their abilities as inhibitors of COVID-19. The findings were streamlined using in silico molecular docking, which revealed promising energy-binding interactions between all flavonoid derivatives and the targeted protein. Notably, compounds 8, 9, 13, and 15 demonstrated higher potency against the coronavirus Mpro protein (PDB ID 6M2N). Compound 8 has a -7.2 Kcal/mol affinity for the protein and binds to it by hydrogen bonding with Gln192 and π-sulfur bonding with Met-165. Compound 9 exhibited a significant interaction with the main protease, demonstrating an affinity of -7.9 kcal/mol. Gln-192, Glu-189, Pro-168, and His-41 were the principle amino acid residues involved in this interaction. The docking score for compound 13 is -7.5 Kcal/mol, and it binds to the protease enzyme by making interactions with Leu-41, π-sigma, and Gln-189. These interactions include hydrogen bonding and π-sulfur. The major protease and compound 15 were found to bind with a favourable affinity of -6.8 Kcal/mol. This finding was further validated through molecular dynamic simulation for 1ns, analysing parameters such as RMSD, RMSF, and RoG profiles. The RoG values for all four of the compounds varied significantly (35.2-36.4). The results demonstrated the stability of the selected compounds during the simulation. After passing the stability testing, the compounds underwent screening for ADME and drug-likeness properties, fulfilling all the necessary criteria. The findings of the study may support further efforts for the discovery and development of safe drugs to treat COVID-19.

Exploring the Mechanism of Myrrh in the Treatment of Breast Cancer Based on Network Pharmacology and Cell Experiments.

This study aimed to investigate the mechanism of action of myrrh in breast cancer (BC) treatment and identify its effective constituents. Data on the compounds and targets of myrrh were collected from the TCMSP, PubChem, and Swiss Target Prediction databases. BC-related targets were obtained from the Genecard database. A protein-protein interaction (PPI) analysis, gene ontology (GO) enrichment, and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were conducted on the intersecting targets of the disease and drug. The key targets of myrrh in BC treatment were identified based on the PPI network. The active constituents of myrrh were determined through reverse-screening using the top 20 KEGG pathways. Macromolecular docking studies, molecular dynamic (MD) simulations, and cell assays were utilized to validate the active constituents and critical targets. Network pharmacology indicated that VEGFA, TP53, ESR1, EGFR, and AKT1 are key targets of myrrh. Pelargonidin chloride, Quercetin, and Naringenin were identified as the active constituents of myrrh. Macromolecular docking showed that Quercetin and Naringenin have strong docking capabilities with ESR1. The results of MD simulation experiments align with those of molecular docking experiments. Cell and western blot assays demonstrated that Quercetin and Naringenin could inhibit MCF-7 cells and significantly reduce the expression of ESR1 protein. The findings reveal the active constituents, key targets, and molecular mechanisms of myrrh in BC treatment, providing scientific evidence that supports the role of myrrh in BC therapy. Furthermore, the results suggest that network pharmacology predictions require experimental validation for reliability.

Antibacterial, Anti-Inflammatory, and Antioxidant Cotton-Based Wound Dressing Coated with Chitosan/Cyclodextrin-Quercetin Inclusion Complex Nanofibers.

Quercetin, recognized for its antioxidant, anti-inflammatory, and antibacterial properties, faces limited biomedical application due to its low solubility. Cotton, a preferred wound dressing material over synthetic ones, lacks inherent antibacterial and wound-healing attributes and can benefit from quercetin features. This study explores the potential of overcoming these challenges through the inclusion complexation of quercetin with cyclodextrins (CDs) and the development of a nanofibrous coating on a cotton nonwoven textile. Hydroxypropyl-beta-cyclodextrin (HP-ß-CD) and hydroxypropyl-gamma-cyclodextrin (HP-γ-CD) formed inclusion complexes of quercetin, with chitosan added to enhance antibacterial properties. Phase solubility results showed that inclusion complexation can enhance quercetin solubility up to 20 times, with HP-γ-CD forming a more stable inclusion complexation compared with HP-ß-CD. Electrospinning of the nanofibers from HP-ß-CD/Quercetin and HP-γ-CD/Quercetin aqueous solutions without the use of a polymeric matrix yielded a uniform, smooth fiber morphology. The structural and thermal analyses of the HP-ß-CD/Quercetin and HP-γ-CD/Quercetin nanofibers confirmed the presence of inclusion complexes between quercetin and each of the CDs (HP-ß-CD and HP-γ-CD). Moreover, HP-ß-CD/Quercetin and HP-γ-CD/Quercetin nanofibers showed a near-complete loading efficiency of quercetin and followed a fast-releasing profile of quercetin. Both HP-ß-CD/Quercetin and HP-γ-CD/Quercetin nanofibers showed significantly higher antioxidant activity compared to pristine quercetin. The HP-ß-CD/Quercetin and HP-γ-CD/Quercetin nanofibers also showed antibacterial activity, and with the addition of chitosan in the HP-γ-CD/Quercetin system, the Chitosan/HP-γ-CD/Quercetin nanofibers completely eliminated the investigated bacteria species. The nanofibers were nontoxic and well-tolerated by cells, and exploiting the quercetin and chitosan anti-inflammatory activities resulted in the downregulation of IL-6 and NO secretion in both immune as well as regenerative cells. Overall, CD inclusion complexation markedly enhances quercetin solubility, resulting in a biofunctional antioxidant, antibacterial, and anti-inflammatory wound dressing through a nanofibrous coating on cotton textiles.

Mechanism of Action of Dihydroquercetin in the Prevention and Therapy of Experimental Liver Injury.

Liver disease is a global health problem that affects the well-being of tens of thousands of people. Dihydroquercetin (DHQ) is a flavonoid compound derived from various plants. Furthermore, DHQ has shown excellent activity in the prevention and treatment of liver injury, such as the inhibition of hepatocellular carcinoma cell proliferation after administration, the normalization of oxidative indices (like SOD, GSH) in this tissue, and the down-regulation of pro-inflammatory molecules (such as IL-6 and TNF-α). DHQ also exerts its therapeutic effects by affecting molecular pathways such as NF-κB and Nrf2. This paper discusses the latest research progress of DHQ in the treatment of various liver diseases (including viral liver injury, drug liver injury, alcoholic liver injury, non-alcoholic liver injury, fatty liver injury, and immune liver injury). It explores how to optimize the application of DHQ to improve its effectiveness in treating liver diseases, which is valuable for preparing potential therapeutic drugs for human liver diseases in conjunction with DHQ.

Potential antioxidant and cytotoxic impacts of defatted extract rich in flavonoids from Styphnolobium japonicum leaves growing in Egypt.

Styphnolobium japonicum leaves are considered a rich source of flavonoids, which are the prospective basis for various therapeutic effects. However, there has been a lack of comprehensive cytotoxic studies conducted on these leaves. Therefore, this ongoing investigation aimed to detect and isolate the flavonoids present in S. japonicum leaves, and assess their antioxidant and anticancer properties. The defatted extract from S. japonicum leaves was analyzed using HPLC, which resulted in the identification of seven phenolics and six flavonoids. Rutin and quercetin were found to be the most abundant. Furthermore, a comprehensive profile of flavonoids was obtained through UPLC/ESI-MS analysis in negative acquisition mode. Fragmentation pathways of the identified flavonoids were elucidated to gain relevant insights into their structural characteristics. Furthermore, genistein 7-O-glucoside, quercetin 3-O-rutinoside, and kaempferol 3-O-α-L-rhamnopyranosyl-(1 → 6)-ß-D-glucopyranosyl-(1 → 2)-ß-D-glucopyranoside were isolated and characterized. The defatted extract rich in flavonoids exhibited significant antioxidant, iron-reducing, free radicals scavenging impacts, and remarkable cytotoxicity against the liver cell line (IC50 337.9µg/ mL) and lung cell line (IC50 55.0 µg/mL). Furthermore, the antioxidant and anticancer capacities of the three isolated flavonoids have been evaluated, and it has been observed that their effects are concentration-dependent. The findings of this research highlight the promising impact of flavonoids in cancer therapy. It is recommended that future scientific investigations prioritize the exploration of the distinct protective and therapeutic characteristics of S. japonicum leaves, which hold significant potential as a valuable natural resource.

The Phytochemical, Quercetin, Attenuates Nociceptive and Pathological Pain: Neurophysiological Mechanisms and Therapeutic Potential.

Although phytochemicals are plant-derived toxins that are primarily produced as a form of defense against insects or microbes, several lines of study have demonstrated that the phytochemical, quercetin, has several beneficial biological actions for human health, including antioxidant and inflammatory effects without side effects. Quercetin is a flavonoid that is widely found in fruits and vegetables. Since recent studies have demonstrated that quercetin can modulate neuronal excitability in the nervous system, including nociceptive sensory transmission via mechanoreceptors and voltage-gated ion channels, and inhibit the cyclooxygenase-2-cascade, it is possible that quercetin could be a complementary alternative medicine candidate; specifically, a therapeutic agent against nociceptive and pathological pain. The focus of this review is to elucidate the neurophysiological mechanisms underlying the modulatory effects of quercetin on nociceptive neuronal activity under nociceptive and pathological conditions, without inducing side effects. Based on the results of our previous research on trigeminal pain, we have confirmed in vivo that the phytochemical, quercetin, demonstrates (i) a local anesthetic effect on nociceptive pain, (ii) a local anesthetic effect on pain related to acute inflammation, and (iii) an anti-inflammatory effect on chronic pain. In addition, we discuss the contribution of quercetin to the relief of nociceptive and inflammatory pain and its potential clinical application.

Ti3C2 MXene quantum dots as an efficient fluorescent probe for bioflavonoid quercetin quantification in food samples.

BACKGROUND: Quercetin (QC) is known as a typical antioxidant as a bioflavonoid, and its quick, sensitive, and specific detection is crucial for assessing food products. In this study, for the purpose of luminescence-based sensing of QC, bright bluish-green emissive quantum dots of N-doped MXene-based titanium carbide (Ti3C2) were fabricated. Recently, MXene quantum dots (MX-QDs), the rapidly emerging zero-dimensional nanomaterials made from two-dimensional transition metal carbides, have attracted much interest due to their unique physical and chemical features. These include the extremely large surface-to-volume ratio, biocompatibility, luminescence tunability, and hybridization capability while retaining properties of their two-dimensional counterpart including good conductivity and charge transferability. RESULTS: The fabricated Ti3C2 MX-QDs had a quantum yield of 8.13 % at the emission wavelength of λem = 465 nm and displayed excellent photostability with great colloidal stability. It was found that introducing QC to near Ti3C2 MX-QDs reduced their fluorescence signals due to quenching effects. These quenching effects that occurred in a very broad linear range of QC (25-600 nM) enabled QC to be sensed quantitatively with the limit of detection of QC (1.35 nM), being the lowest ever reported to date. The quenching phenomena that caused such excellent sensitivity could be accounted for by combined effects of static quenching/radiation-free complex formation and inner filter effects (IFE) of Ti3C2 MX-QDs with QC. SIGNIFICANCE: In addition, the quenching-based detection demonstrated excellent specificity against structurally relevant interferants. Therefore, the presented sensing strategies with Ti3C2 MX-QDs-based fluorescence quenching can be one of the strongest candidates as a reliable and cost-effective solution to highly sensitive quantification of QC in food samples.

6-Carboxycellulose Acetate Butyrate: Effectiveness as an Amorphous Solid Dispersion Polymer.

Amorphous solid dispersion (ASD) in a polymer matrix is a powerful method for enhancing the solubility and bioavailability of otherwise crystalline, poorly water-soluble drugs. 6-Carboxycellulose acetate butyrate (CCAB) is a relatively new commercial cellulose derivative that was introduced for use in waterborne coating applications. As CCAB is an amphiphilic, carboxyl-containing, high glass transition temperature (Tg) polymer, characteristics essential to excellent ASD polymer performance, we chose to explore its ASD potential. Structurally diverse drugs quercetin, ibuprofen, ritonavir, loratadine, and clarithromycin were dispersed in CCAB matrices. We evaluated the ability of CCAB to create ASDs with these drugs and its ability to provide solubility enhancement and effective drug release. CCAB/drug dispersions prepared by spray drying were amorphous up to 25 wt % drug, with loratadine remaining amorphous up to 50% drug. CCAB formulations with 10% drug proved effective at providing in vitro solubility enhancement for the crystalline flavonoid drug quercetin as well as ritonavir, but not for the more soluble APIs ibuprofen and clarithromycin and the more hydrophobic loratadine. CCAB did provide slow and controlled release of ibuprofen, offering a simple and promising Long-duration ibuprofen formulation. Formulation with clarithromycin showed the ability of the polymer to protect against degradation of the drug at stomach pH. Furthermore, CCAB ASDs with both loratadine and ibuprofen could be improved by the addition of the water-soluble polymer poly(vinylpyrrolidone) (PVP), with which CCAB shows good miscibility. CCAB provided solubility enhancement in some cases, and the slower drug release exhibited by CCAB, especially in the stomach, could be especially beneficial, for example, in formulations containing known stomach irritants like ibuprofen.

Coadministration of Quercetin and Indocyanine Green via PEGylated Phospholipid Micelles for Augmented Chem-Photothermal Combination Tumor Therapy.

A significant impediment persists in developing multicomponent nanomedicines designed to dismantle the heat shock protein (HSP)-based protective mechanism of malignant tumors during photothermal therapy. Herein, well-defined PEGylated phospholipid micelles were utilized to coencapsulate quercetin (QUE, a natural anticancer agent and potent HSP inhibitor) and indocyanine green (ICG, a photothermal agent) with the aim of achieving synchronized and synergistic drug effects. The subsequent investigations validated that the tailored micellar system effectively enhanced QUE's water solubility and augmented its cellular internalization efficiency. Intriguingly, the compositional PEGylated phospholipids induced extraordinary endoplasmic reticulum stress, thereby sensitizing the tumor cells to QUE. Furthermore, QUE played a crucial role in inhibiting the stress-induced overexpression of HSP70, thereby augmenting the photothermal efficacy of ICG. In systemic applications, the proposed nanotherapeutics exhibited preferential accumulation within tumors and exerted notable tumoricidal effects against 4T1 xenograft tumors under 808 nm near-infrared irradiation, facilitated by prominent near-infrared fluorescence imaging-guided chemo-photothermal therapy. Therefore, our strategy for fabricating multicomponent nanomedicines emerges as a coordinated platform for optimizing antitumor therapeutic efficacy and offers valuable insights for diverse therapeutic modalities.

Evaluation of the release kinetics of hydrophilic and lipophilic compounds from lipid-polymer hybrid nanoparticles.

In disease treatment, maintaining therapeutic drug concentrations often requires multiple doses. Lipid/polymer hybrid nanoparticles (LPHNPs) offer a promising solution by facilitating sustained drug delivery within therapeutic ranges. Here, we synthesized poly(lactic-co-glycolic acid) (PLGA) nanoparticles coated with soy lecithin using nanoprecipitation and self-assembly techniques. These nanoparticles were incorporated into gelatin aerogels to ensure uniform distribution and increase the concentration. Our study focused on understanding the release kinetics of hydrophilic (gallic acid) and lipophilic (quercetin) compounds from this system. Nanoparticles exhibited hydrodynamic diameters of 100 ± 15 nm (empty), 153 ± 33 nm (gallic acid-loaded), and 149 ± 21 nm (quercetin-loaded), with encapsulation efficiencies of 90 ± 5% and 70 ± 10% respectively. Gallic acid release followed the Korsmeyer-Peppas kinetics model (n = 1.01), while quercetin showed first-order kinetics. Notably, encapsulated compounds demonstrated delayed release compared to free compounds in gelatin aerogels, illustrating LPHNPs' ability to modulate release profiles independent of the compound type. This study underscores the potential of LPHNPs in optimizing drug delivery strategies for enhanced therapeutic outcomes.

Feasibility of the inhibitor development for cancer: A systematic approach for drug design.

The traditional Chinese medicine (TCM) bupleurum-ginger-licorice formula presents significant anti-cancer effects, but its active ingredients and inhibitory mechanism remain unclear. In this work, the core effective ingredient quercetin and its signal transducer and activator of transcription 3 (Stat3) receptor both were identified by network pharmacology. Quercetin is a low-toxicity, non-carcinogenic flavonoid with antioxidant, anti-inflammatory and anticancer activities, which is widely distributed in edible plants. Stat3 can bind to specific DNA response elements and serves as a transcription factor to promote the translation of some invasion/migration-related target genes, considered as a potential anticancer target. Here, molecular docking and molecular dynamics (MD) simulation both were used to explore molecular recognition of quercetin with Stat3. The results show that quercetin impairs DNA transcription efficiency by hindering Stat3 dimerization, partially destroying DNA conformation. Specifically, when the ligand occupies the SH2 cavity of the enzyme, spatial rejection is not conductive to phosphokinase binding. It indirectly prevents the phosphorylation of Y705 and the formation of Stat3 dimer. When the inhibitor binds to the DT1005 position, it obviously shortens the distance between DNA and DBD, enhances their binding capacity, and thereby reduces the degree of freedom required for transcription. This work not only provides the binding modes between Stat3 and quercetin, but also contributes to the optimization and design of such anti-cancer inhibitors.

Enhanced anti-tumor and anti-metastatic activity of quercetin using pH-sensitive Alginate@ZIF-8 nanocomposites:in vitroandin vivostudy.

Quercetin (Qc) possesses anti-cancer properties, such as cell signaling, growth suppression, pro-apoptotic, anti-proliferative, and antioxidant effects. In this study, we developed an alginate-modified ZIF-8 (Alg@ZIF-8) to enhance the anti-tumor efficacy of Qc. The developed alginate-modified quercetin-loaded ZIF-8 (Alg@Qc@ZIF-8) was characterized using scanning electron microscope (SEM), dynamic light scattering (DLS), fourier transform infrared spectroscopy Thermogravimetric analysis, Brunauer-Emmett-Teller, and x-ray diffraction. The drug release pattern was evaluated at pH 5.4 and 7.4. The cytotoxicity of nanoparticles was assessed on the 4T1 cell line. Finally, the anti-tumor activity of Alg@Qc@ZIF-8 was evaluated in 4T1 tumor-bearing mice. SEM showed that the nanoparticles were spherical with a diameter of mainly below 50 nm. The DLS showed that the developed nanoparticles' hydrodynamic diameter, zeta potential, and polydispersity index were 154.9 ± 7.25 nm, -23.8 ± 5.33 mV, and 0.381 ± 0.09, respectively. The drug loading capacity was 10.40 ± 0.02%. Alg@Qc@ZIF-8 exhibited pH sensitivity, releasing more Qc at pH 5.4 (about 3.62 times) than at pH 7.4 after 24 h. Furthermore, the IC50value of Alg@Qc@ZIF-8 on the 4T1 cell line was 2.16 times lower than net Qc. Importantly, in tumor-bearing mice, Alg@Qc@ZIF-8 demonstrated enhanced inhibitory effects on tumor growth and lung metastasis compared to net Qc. Considering thein vitroandin vivooutcomes, Alg@Qc@ZIF-8 might hold great potential for effective breast cancer management.

Co-encapsulation of vitamin E and quercetin by soybean lipophilic proteins based on pH-shifting and ultrasonication: Focus on interaction mechanisms, structural and physicochemical properties.

This study explored the mechanism of interaction of pH-shifting combined ultrasonication and its effect on soybean lipophilic proteins (SLP) and the potential of modified SLP as the carrier for vitamin E (VE) and quercetin (QU). The spectroscopy results revealed that both VE and QU changed the SLP conformation and exposed hydrophobic groups. The loading rates of VE and QU by SLP with alkaline pH-shifting combined with ultrasonication (300 w,20 min) were 86.91% and 75.99%, respectively. According to the antioxidant analysis, with an increase in the ultrasonication power, the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) radical scavenging capacity of the samples increased, where the DPPH and ABTS radical scavenging capacity of sample SQV-6 were 70.90% and 63.43%, respectively. The physicochemical properties, microstructure, and stability of the SLP-VE-QU complex improved significantly. Overall, the present findings broadened the application of simple structural carriers for co-encapsulating functional factors.

Highly functionalized pH-triggered supramolecular nanovalve for targeted cancer chemotherapy.

Chemotherapeutic drug delivery systems are commonly limited by their short half-lives, poor bioavailability, and unsuccessful targetability. Herein, pH-responsive hybrid NPs consist of benzimidazole-coated mesoporous silica nanoparticles (BZ-MSN) loaded with naturally occurring flavonoid quercetin (QUE-BZ-MSN). The NPs were further capped with beta-cyclodextrin (BCD) to obtain our desired BCD-QUE-BZMSN, with a zeta potential around 7.05 ± 2.37 mV and diameter about 115.2 ± 19.02 nm. The abundance of BZ onto the nanoparticles facilitates targeted quercetin chemotherapy against model lung and liver cancer cell lines. FTIR, EDX, and NMR analyses revealed evidence of possible surface functionalizations. Powder XRD analysis showed that our designed BCD-QUE-BZMSN formulation is amorphous in nature. The UV and SEM showed that our designed BCD-QUE-BZMSN has high drug entrapment efficiency and a nearly spherical morphology. In vitro, drug release assessments show controlled pH-dependent release profiles that could enhance the targeted chemotherapeutic response against mildly acidic regions in cancer cell lines. The obtained BCD-QUE-BZMSN nanovalve achieved significantly higher cytotoxic efficacy as compared to QUE alone, which was evaluated by in vitro cellular uptake against liver and lung cancer cell lines, and the cellular morphological ablation was further confirmed via inverted microscopy. The outcomes of the study imply that our designed BCD-QUE-BZMSN nanovalve is a potential carrier for cancer chemotherapeutics.

Quercetin-loaded melanin nanoparticle mediated konjac glucomannan/polycaprolactone bilayer film with dual-mode synergistic bactericidal activity for food packaging.

It is still difficult for a single antibacterial modality to realize satisfactory management of bacterial breeding in food preservation. To solve this problem, we developed a photothermal-derived dual-mode synergistic bactericidal konjac glucomannan (KGM)/polycaprolactone (PCL) bilayer film incorporated with quercetin-loaded melanin-like nanoparticles (Q@MNPs). The results showed that the mechanical properties (TS: 29.8 MPa, EAB: 43.1 %), UV shielding properties, and water resistance (WCA: 124.1°, WVP: 3.92 g mm/m2 day kPa) of KGM-Q@MNPs/PCL bilayer films were significantly improved. More importantly, KGM-Q@MNPs/PCL bilayer film presented outstanding photothermal inversion and controlled release behavior of Q triggered by near infrared (NIR) radiation, thus contributing to excellent dual-mode synergistic antibacterial properties against E. coli and S. aureus. Meanwhile, the KGM-Q@MNPs/PCL bilayer film possessed good biocompatibility and low toxicity. As a proof-of-concept application, we further verified the significant value of film for the preservation of cherry tomatoes. Since KGM-Q@MNPs/PCL bilayer film showed excellent biodegradability, this work will aid the development of sustainable antibacterial food packaging materials.