Interaction of Pyrogallol-Containing Polyphenols with Mucin Reinforces Intestinal Mucus Barrier Properties.

High consumption of polyphenol-rich green tea, coffee, fruits, and vegetables is associated with a low risk of human chronic diseases. Recent studies highlight the relevance of polyphenol-mediated gut microbiota modulation and its impact on mucus barrier. Herein, we study the direct interaction of epicatechin (EC), epigallocatechin gallate (EGCG), and tannic acid (TA) with intestinal mucin by isothermal titration calorimetry and multiple particle tracking and the impact on mucus barrier using ex vivo mucus and Caco-2/HT29-MTX cocultures. Results show that pyrogallol-containing polyphenols EGCG and TA exhibit strong binding to intestinal mucin and reinforce mucus barrier, whereas EC does not. ECGG and TA also mitigate gliadin-mediated cytotoxicity and inflammation. The chemical binding of EGCG and TA to the nucleophilic thiol groups of mucins shows their roles as cross-linkers of mucin networks. These results bring a novel understanding of the health benefits of polyphenols and provide support for the consumption of pyrogallol-containing beverages like green tea as a potential dietary therapy for gluten-related disorders.

Multifunctional nanocarrier with self-catalytic production of nitric oxide for photothermal and gas-combined therapy of tumor.

Single treatment often faces the problem that it cannot completely eradicate tumor and inhibit the tumor metastasis. In order to overcome this shortcoming, multi-modal tumor treatment has attracted widespread attention. In the present article, based on ascorbyl palmitate (PA) and l-arginine (l-Arg), a multifunctional nanocarrier is designed for synergetic treatment of tumor with photothermal and nitric oxide (NO) gas therapy. Firstly, PA and l-Arg were self-assembled to form novel functional micelles, PL, with high biosafety using electrostatic interaction and hydrogen bonding. The functional micelles could self-catalyze to produce NO at the tumor site. Then, Ag2S quantum dots having fluorescence imaging and photothermal properties were encapsulated to obtain the nanocarrier, A@PL. The results show that A@PL had a hydrated size of around 78 nm and presented good stability within 30 d. Moreover, in vitro studies indicate that it was efficient with regards to NO self-generating capacity, whereas the photothermal conversion efficiency was as high as 34% under near-infrared light irradiation. The cytotoxicity results show that, when the concentration of A@PL was as high as 2 mM, the survival rate of 3 T3 cells was still 78.23%, proving that the probe has good safety characteristics. Fluorescence imaging results show that its maximum enrichment can be achieved at the tumor site after tail vein injection for 3 h, and out of the body after 24 h, indicating good internal circulation. The in vivo studies show that the rate of inhibition of tumor using the nanocarrier was as high as 98%, and almost overcame the problem of tumor recurrence caused by single treatment, thus presenting a significant tumor treatment effect. This new multifunctional nanocarrier with self-catalytic production of NO provides a new idea for the efficient treatment of tumors.

Pectin gels based on H+/(NH4)2SO4 and its potential in sustained release of NH4.

A gelling strategy for HP was proposed in this study, ammonium sulfate (AS) as a co-solute could induce the gelling of HP in acidic environment. The solubility and Zeta potential of HP dramatically decreased in AS solution, which indicated AS could promote the aggregation of HP. The rheological results confirmed the gelling of HP (G' > G″) with AS: 25-30 wt% and pH ≤ 3.0, and the gel strength is mainly depended on HP rather than AS concentration. Smaller AS crystals (SEM) and reduced T2 values (LF-NMR) were observed in HP gels, suggested the gel network of HP could limit the migration of AS and water. Finally, it was found that the release process of NH4+ in HP + AS gel was lagged behind that of pure AS, which verified the potential of HP + AS gel in the field of sustained-release fertilizers.

Physicochemical characteristics and functional properties of high methoxyl pectin with different degree of esterification.

Moderate alkali de-esterification can change the physicochemical characteristics and thus the functional properties of high methoxyl pectin (HMP). The results revealed that de-esterification could increase negative charges (Zeta potential from -21 to -31 mV), decrease molecular weight (from 448 to 136 kDa) and apparent viscosity of HMP. Homogalacturonan (HG) content decreased (from 62% to 49%) while rhamnogalacturonan Ⅰ (RG-Ⅰ) content increased (from 32% to 46%) after de-esterification. The group characteristics of HMP with different degree of esterification (DE) were similar and no obvious impact was made on degree of crystallinity by alkali de-esterification. A conformation transition of HMP molecule implied by Congo red test were occurred as the DE decreased. With the decrease of DE, the molecular structure of HMP became shorter and smaller, and the entanglement was weaker. The de-esterification caused slight decrease of thermal stability. Alkali de-esterification would weaken the gel property and the emulsifying ability of HMP.

Curcumin loaded sub-30 nm targeting therapeutic lipid nanoparticles for synergistically blocking nasopharyngeal cancer growth and metastasis.

Systemic chemotherapy is still the primary treatment for advanced-stage nasopharyngeal carcinoma (NPC), but only limited therapeutic success has been achieved in the past decade because of drug resistance and systemic toxicity. Curcumin (Cur) is an effective alternative to chemotherapeutics because it showed remarkable therapeutic potential in the treatment of NPC. However, lack of tissue specificity and poor penetration in solid tumors are the major obstacles to effective therapy. Therefore, in this work, a self-assembled sub-30 nm therapeutic lipid nanoparticle loaded with Cur, named as Cur@α-NTP-LN, was constructed, specifically targeting scavenger receptor class B member 1 (SR-B1) and enhancing its therapeutic effects on NPC in vivo. Our results showed that Cur@α-NTP-LNs were effective and superior to free Cur on NPC cell-specific targeting, suppressing cell proliferation and inducing cell apoptosis. In vivo and ex vivo optical imaging revealed that Cur@α-NTP-LNs exerted high targeting efficiency, specifically accumulating in NPC xenograft tumors and delivering Cur into the tumor center after systemic administration. Furthermore, Cur@α-NTP-LNs exhibited a remarkable inhibitory effect on the growth of NPC subcutaneous tumors, with over 71 and 47% inhibition compared to Cur- and α-NTP-LNs-treated groups, respectively. In addition, Cur@α-NTP-LNs almost blocked NPC metastasis in a lung metastasis model of NPC and significantly improved the survival rate. Thus, the sub-30 nm Cur@α-NTP-LNs enhanced the solubility of Cur and demonstrated the ability of targeted Cur delivery into the center of the solid NPC tumor, performing synergistic inhibitory effects on the growth of NPC tumor and its metastasis with high efficiency.

Identification of Tibetan medicine Dida based on DNA barcoding.

The purpose of this study was to test the ability of DNA barcoding to identify the herbal raw trade of Tibetan medicine Dida in China. A reference database for plant-material DNA barcodes was successfully constructed and used to identify 36 commercially samples of Dida collected from Southwest China. The ITS sequence was amplified from these samples and the efficiency of the PCR amplification of ITS was 100%. The DNA sequencing results revealed that 3 samples (8.3%) were authenticated as Swertia chirayita, 2 sequences (5.6%) were authenticated as Swertia mussotii, 3 sequences (8.3%) were authenticated as Swertia ciliata, as recorded in the Tibetan Pharmacopeia. The other samples were authenticated as adulterants and all of them originated from common plants belonging to Saxifraga, Swertia and Halenia. This result indicates Dida pieces that are available in the market have complex origins and may indicate a potential safety issue and DNA barcoding is a convenient tool for market supervision.

Structural characterization of pectin-bismuth complexes and their aggregation in acidic conditions.

Bismuth-contained therapies are effective in treating gastric ulcer and eliminating Helicobacter pylori (Hp). Anion polysaccharides ligand could reduce the intake of bismuth, and enhance drug efficacy of bismuth compounds. In this study, pectin-bismuth (PB) was prepared and the changes of PB structure in acidic environment were reported for the first time. The structure of PB was characterized by FT-IR, XRD, and TGA, which suggested that combined with bismuth could alter the crystal structure of pectin. XPS confirmed the ionic binding of Bi3+ with carboxyl groups of pectin. The aggregating of PB with different pH level were also investigated, and the influence of pH on PB structure were observed by SEM. Results showed that PB has much larger volume of flocculation in acidic environment compared with bismuth nitrate. Additionally, apparent shear stress (τa) of PB suspension was evaluated. These results revealed the structural characteristics and acid-induced aggregation of pectin-bismuth, and bismuth could aggregate in acidic solution with the gelation of pectin.

Food-Grade Emulsions and Emulsion Gels Prepared by Soy Protein-Pectin Complex Nanoparticles and Glycyrrhizic Acid Nanofibrils.

Glycyrrhizic acid (GA) and GA nanofibrils (GN) have been shown to be efficient natural emulsifiers for formation and stabilization of food emulsions. In this work, the emulsion properties of GN in the presence of soy protein isolate-pectin complex nanoparticles (SPNPs) were studied to understand the impact of the nanofibril-nanoparticle interactions on emulsion stabilization. In the presence of low GN concentrations (0.1-0.5 wt %), the synergy in reducing the interfacial tension was observed due to SPNPs-GN complexation in the bulk and at the interface by hydrogen bonding, endowing the prepared emulsions with an overall smaller droplet size. However, obvious flocculation and clustering of oil droplets occurred in these emulsions (especially at 0.25 and 0.5 wt % GN), which are probably induced by a depletion mechanism. At high GN concentrations (1-2 wt %), due to the preferential adsorption, the GN mainly dominated the interface and the subsequent formation and properties of emulsions. Accordingly, the self-standing emulsion gels were obtained, showing a small droplet size with d32 of about 1.0-1.5 µm, homogeneous appearance and microstructure, and encouraging rheological properties including high gel strength, shear sensitivity, and good thixotropic recovery. This is mainly attributed to the formation of a fibrillar hydrogel network in the continuous phase as well as around the droplet surfaces.

Properties of dietary fiber from citrus obtained through alkaline hydrogen peroxide treatment and homogenization treatment.

In this research, citrus dietary fiber (CF) was modified by two methods, homogenization or alkalinehydrogenperoxide (chemical) treatment, to improve its physicochemical properties. The homogenization and chemical treatment highly increased the CF's water swelling capacity by 433% and 276%, respectively. The water holding capacity of CF significantly increased by 253% after homogenization and 197% after chemical treatment. Both treatments increased CF's total dietary fiber content and thermal stability. Moreover, the chemically treated CF thermal stability was higherthan the homogenized one. Scanning electron microscopy (SEM) results showed the modified CFs exhibited porous structure. XRD and NMR results showed that the CF's crystalline region could be disrupted by both treatments. Overall results suggest that the two treatments could effectivelyimprove CF physicochemical properties. The modified fibers might be potentially used as functional food ingredients.

Regulation of redox balance using a biocompatible nanoplatform enhances phototherapy efficacy and suppresses tumor metastasis.

Many cancer treatments including photodynamic therapy (PDT) utilize reactive oxygen species (ROS) to kill tumor cells. However, elevated antioxidant defense systems in cancer cells result in resistance to the therapy involving ROS. Here we describe a highly effective phototherapy through regulation of redox homeostasis with a biocompatible and versatile nanotherapeutic to inhibit tumor growth and metastasis. We systematically explore and exploit methylene blue adsorbed polydopamine nanoparticles as a targeted and precise nanocarrier, oxidative stress amplifier, photodynamic/photothermal agent, and multimodal probe for fluorescence, photothermal and photoacoustic imaging to enhance anti-tumor efficacy. Remarkably, following the glutathione-stimulated photosensitizer release to generate exogenous ROS, polydopamine eliminates the endogenous ROS scavenging system through depleting the primary antioxidant, thus amplifying the phototherapy and effectively suppressing tumor growth in vitro and in vivo. Furthermore, this approach enables a robust inhibition against breast cancer metastasis, as oxidative stress is a vital impediment to distant metastasis in tumor cells. Innovative, safe and effective nanotherapeutics via regulation of redox balance may provide a clinically relevant approach for cancer treatment.

A near-infrared light-controlled smart nanocarrier with reversible polypeptide-engineered valve for targeted fluorescence-photoacoustic bimodal imaging-guided chemo-photothermal therapy.

Despite burgeoning development of nanoplatform made in the past few years, it remains a challenge to produce drug nanocarrier that enables requested on/off drug release. Thus, this study aimed to develop an ideal near-infrared light-triggered smart nanocarrier for targeted imaging-guided treatment of cancer that tactfully integrated photothermal therapy with chemotherapy to accurately control drug release time and dosage. Methods: This delivery system was composed of Ag2S QD coating with dendritic mesoporous silica (DMSN), which acted as nanocarrier of doxorubicin localized inside pores. To provide the nanocarrier with controlled release capability, a polypeptide-engineered that structure was reversible to photothermal effect of Ag2S QD, was covalently grafted to the external surface of drug-loaded DMSN. Results: This nanocarrier with the size of 40~60 nm had satisfactory biocompatibility and photothermal conversion efficiency up to 28.35%. Due to acidity-triggered charge reversal of polypeptide, which significantly extended circulation time and improved targeting ability, fluorescence and photoacoustic signals were still obvious at tumor site post-24 h by tail vein injection and chemo-photothermal synergistic therapy obviously enhanced antitumor efficacy. Mild PTT with multiple short-term exposures not only reduced the side effect of overdose drug but also avoided skin damage caused by long-term irradiation. Conclusion: By adjusting irradiation time and on/off cycle, multiple small amount local drug release reduced the side effect of overdose drug and skin damage. This novel approach provided an ideal near-infrared light-triggered nanocarrier with accurate control of area, time, and especially dosage.

Fabrication of Novel Hierarchical Multicompartment Highly Stable Triple Emulsions for the Segregation and Protection of Multiple Cargos by Spatial Co-encapsulation.

High-order multiple emulsions are of great interest in both fundamental research and industrial applications as vehicles for their encapsulation capability of actives. In this work, we report a hierarchically multicompartmental highly stable triple emulsion by emulsifying and assembling of natural Quillaja saponin. Water-in-oil-in-(oil-in-water) (W2/O2/(O1/W1)) triple emulsion indicates that the compartmented system consisted of surfaced saponin-coated nanodroplets (SNDs) and dispersed oil globules, which in turn contained smaller aqueous droplets. The effects of formulation parameters, including lipophilic emulsifier content, oil fraction, and SND concentration, on the formation of multiple emulsions were systematically investigated. The assembly into fibrillar network of SNDs at the outer oil-water interface effectively protected the triple emulsion droplets against flocculation and coalescence, and strongly prevented the osmotic-driven water diffusion between the internal water droplets and the external water phase, thus contributing to superior stability during 180 days storage. All of these characteristics make the multicompartmentalized emulsions suitable to co-encapsulate a hydrophilic bioactive (gardenia blue) and two hydrophobic bioactives (eapsanthin and curcumin) in a single emulsion droplet hierarchically for the segregation and protection of multiple cargos. This approach offers a promising route toward accessing the next generation of functional deliveries and encapsulation strategies.

Protein-Based Pickering High Internal Phase Emulsions as Nutraceutical Vehicles of and the Template for Advanced Materials: A Perspective Paper.

Pickering high internal phase emulsions (HIPEs) are normally highly concentrated emulsions stabilized by colloidal particles with a minimum internal phase volume fraction of 0.74. They have received considerable attention in many fields, including pharmaceuticals, tissue engineering, foods, and personal care products. The aim of this perspective is to update the current knowledge on the field of protein-based Pickering HIPEs, emphasizing those aspects that need to be explored and clarified. Research progress in constructing HIPEs by protein-type colloid particles and promising research trends in basic research and potential applications were highlighted. Promising studies in this field include (1) clarifying bioavailability and evolution of activity of active ingredients in Pickering HIPEs by oral administration, (2) constructing a Pickering interfacial catalysis platform using protein colloidal particles, and (3) expanding the emerging applications of Pickering HIPEs in fields, such as partially hydrogenated oil replacers, probiotic encapsulation, and the template for porous materials.

An injectable hybrid hydrogel based on a genetically engineered polypeptide for second near-infrared fluorescence/photoacoustic imaging-monitored sustained chemo-photothermal therapy.

An injectable multifunctional hydrogel based on an engineered coiled-coil polypeptide, Ag2S quantum dots (QDs), and paclitaxel (PTX) has been developed for sustained chemo-photothermal therapy. Oil-soluble Ag2S QDs and PTX were first loaded into nanogels formed with engineered polypeptide PC10A by ultrasonic treatment to prepare PC10A/Ag2S QD/PTX nanogels. The multifunctional PC10A/Ag2S QD/PTX hydrogels were prepared by dissolving the PC10A/Ag2S QD/PTX nanogels into the PC10A hydrogel. The PC10A/Ag2S QD/PTX hydrogel can be injected directly into the site of tumors. In vitro and in vivo toxicity results showed that the PC10A/Ag2S QD/PTX hydrogel presented excellent biocompatibility. Compared with single near-infrared photothermal therapy and chemotherapy, the combined therapy could effectively suppress the growth of SKOV3 ovarian carcinoma tumor. In addition, real-time monitoring of the in vivo degradation of the PC10A/Ag2S QD/PTX hydrogel was achieved by near-infrared fluorescence imaging and photoacoustic imaging. These results demonstrated that this injectable multifunctional PC10A/Ag2S QD/PTX hydrogel has the potential as a theranostic platform for sustained cancer treatments.

A Simple Glutathione-Responsive Turn-On Theranostic Nanoparticle for Dual-Modal Imaging and Chemo-Photothermal Combination Therapy.

Constructing a tumor microenvironment stimuli activatable theranostic nanoparticle with simple components and preparation procedures for multimodality imaging and therapy remains a major challenge for current theranostic systems. Here we report a novel and simple glutathione (GSH)-responsive turn-on theranostic nanoparticle for dual-modal imaging and combination therapy. The theranostic nanoparticle, DHP, consisting of a disulfide-bond-linked hydroxyethyl starch paclitaxel conjugate (HES-SS-PTX) and a near-infrared (NIR) cyanine fluorophore DiR, is prepared with a simple one-step dialysis method. As DiR is encapsulated within the hydrophobic core formed by HES-SS-PTX, the fluorescence of DiR is quenched by the aggregation-caused quenching (ACQ) effect. Nonetheless, once DHP is internalized by cancer cells, the disulfide bond of HES-SS-PTX can be cleaved by intracellular GSH, leading to the synchronized release of conjugated PTX and loaded DiR. The released PTX could exert its therapeutic effect, while DiR could adsorb onto nearby endosome/lysosome membranes and regain its fluorescence. Thus, DHP could monitor the release and therapeutic effect of PTX through the fluorescence recovery of DiR. Remarkably, DHP can also be used as an in vivo probe for both fluorescent and photoacoustic imaging and at the same time achieves potent antitumor efficacy through chemo-photothermal combination therapy. This study provides novel insights into designing clinically translatable turn-on theranostic systems.

Multicompartment emulsion droplets for programmed release of hydrophobic cargoes.

Delivery systems with multicompartmental structures that allow simultaneous delivery of several cargos are of great interest in both fundamental research and industrial applications. Here, we report a facile and easily scalable approach to fabricate multi-compartmentalized microdroplets for achieving programmed release of hydrophobic cargoes. Well-dispersed nanodroplets stabilized by natural Quillaja saponin served as an effective colloid stabilizer for fabricating microscale emulsion droplets with multicompartment architectures comprising many nanoscale droplets as a shell and single microscale core. Control of the number of nanodroplets allows accurate manipulation of the interface permeability for flexible and controllable release of volatile compounds (e.g., 2,3-butanedione, cis-3-hexen-1-ol, ethyl butyrate, d-limonene). More interestingly, the multicompartment microdroplets exhibited a higher flexibility for programmed release of different volatile compounds, as well as curcumin, during in vitro digestion by introducing cargos into the shell subcompartments or core microcompartment. The promising results highlight the power of this multi-compartmentalized system toward accessing a powerful platform for functional cargo delivery strategies.

Salt reduction in liquid/semi-solid foods based on the mucopenetration ability of gum arabic.

Salt reduction in liquid/semi-solid processed foods remains a significant challenge as these foods contribute mostly to the high dietary sodium intake in our daily life. From the results of a taste contrast and quantitative saltiness analysis with trained panels, we found that the addition of high amounts of gum arabic could enhance the saltiness perception of standard NaCl solution and enable a 30% reduction of salt in yogurt drink and mayonnaise without impacting the saltiness perception. Via in vitro sodium retention experiments conducted using ex vivo porcine tongue, simulated tongue and Transwell methods, we suggested that the enhanced saltiness and sodium retention on the mucosa were possibly due to the mucopenetration ability of gum arabic. This finding would be useful for the design of low-salt liquid/semi-solid foods and has implications for novel food formulations to enhance flavor and nutrient delivery.

Fabrication and Characterization of Novel Water-Insoluble Protein Porous Materials Derived from Pickering High Internal-Phase Emulsions Stabilized by Gliadin-Chitosan-Complex Particles.

Pickering high internal-phase emulsions (HIPEs) and porous materials derived from the Pickering HIPEs have received increased attention in various research fields. Nevertheless, nondegradable inorganic and synthetic stabilizers present toxicity risks, thus greatly limiting their wider applications. In this work, we successfully developed nontoxic porous materials through the Pickering HIPE-templating process without chemical reactions. The obtained porous materials exhibited appreciable absorption capacity to corn oil and reached the state of saturated absorption within 3 min. The Pickering HIPE templates were stabilized by gliadin-chitosan complex particles (GCCPs), in which the volume fraction of the dispersed phase (90%) was the highest of all reported food-grade-particle-stabilized Pickering HIPEs so far, further contributing to the interconnected pore structure and high porosity (>90%) of porous materials. The interfacial particle barrier (Pickering mechanism) and three-dimensional network formed by the GCCPs in the continuous phase play crucial roles in stabilization of HIPEs with viscoelastic and self-supporting attributes and also facilitate the development of porous materials with designed pore structure. These materials, with favorable biocompatibility and biodegradability, possess excellent application prospects in foods, pharmaceuticals, materials, environmental applications, and so on.

Characterization of Orange Oil Powders and Oleogels Fabricated from Emulsion Templates Stabilized Solely by a Natural Triterpene Saponin.

A new facile route was reported to use the natural triterpene Quillaja saponin (QS)-stabilized orange emulsions as a template for the development of flavor oil powders and oleogels achieved by the tunable oil fraction and drying mode. A fibrosis network interfacial film from self-assembly of QS at the oil-water interface possibility contributed to the fabrication of stable emulsion precursors and subsequent oil powder and oleogels by packing oil droplets in the network structure. An oil powder containing as high as 93 wt % orange oil was obtained by spray drying, showing excellent stability, flowability, and reconstitution ability. Upon the medium water removal rate of freeze drying, porous structured solid products followed by oleogels by a simple shearing can be formed. Upon oven drying, a translucent oleogel with high oil loading of 98.2 wt % was obtained from the high internal phase emulsion template. The resulting oleogels showed tunable rheological and texture properties, thixotropic recovery by modulating the oil fraction and water evaporation rate, and reversibility to reconstituted emulsions. Structuring liquid oil into solid materials by simply drying the continuous water from solely QS-based emulsions is very encouraging and provides new insights into various functional applications in the fields of foods, pharmaceuticals, cosmetics, and agriculture.

Dry fractionation of surface abrasion for polyphenol-enriched buckwheat protein combined with hydrothermal treatment.

Buckwheat constitutes a good source of bioactive components. A dry fractionation of surface abrasion for polyphenol-enriched protein combined with hydrothermal treatment was evaluated as an alternative to conventional wet extraction from tartary buckwheat (Fagopyrum esculentum Moench). The protein contents and the total polyphenol contents of both free and bound polyphenol gradually decreased in the order from the outer to the inner fractions. Polyphenol-enriched buckwheat protein flour was successfully enrichment with a maximum polyphenol content of 55 mg/g. Moreover, starch digestibility and polyphenols bioaccessibility of the buckwheat protein were increased with hydrothermal treatment time, while protein digestibility decreased slightly. Besides, most of the aroma compounds increased during the hydrothermal treatment. The assessment results demonstrate that the sustainability dry surface abrasion process in combination with hydrothermal treatment should be encouraged in processing functional protein fractions and improving both qualities of end use products and health benefits.