The thermal resistance and targeting release of zein-sodium alginate binary complexes as a vehicle for the oral delivery of riboflavin.

Riboflavin (RF) is one kind of vitamin B, which has low bioavailability due to the low water solubility and the high photosensitivity during food processing and storage. The anti-solvent precipitation method was applied to fabricate a zein-sodium alginate (SA) binary complexes delivery system with the loading of RF, which was aimed to enhance the delivery efficiency, stability, and controlled release of RF in the gastrointestinal (GI) tract. The formation mechanism, physicochemical properties as well as the digestion behaviors were investigated. The incorporation of SA significantly increased the diameter and decreased the surface positive charge of the nanoparticles. The surface morphology of the nanoparticles was characterized using the scanning electron microscope. The FTIR analysis revealed that the electrostatic attraction was the dominant binding force in the formation of the zein-SA binary complexes nanoparticles. In addition, the study on the in vitro release process showed that the zein-SA nanoparticles could delay the release of the RF under the simulated GI tract conditions, which improved their oral bioavailability. In summary, the zein-SA nanoparticle is an effective vehicle for the oral delivery of RF as well as other vitamins and bioactives in the applications of food and nutrition.

Overproduced CPSF4 Promotes Cell Proliferation and Invasion via PI3K-AKT Signaling Pathway in Oral Squamous Cell Carcinoma.

PURPOSE: Invasion and metastasis are major challenges in the treatment of oral cancer. We hypothesize that cleavage and polyadenylation specific factor 4 (CPSF4), a key mediator of cell growth and metastasis in several types of cancers, contributes to oral squamous cell carcinoma (OSCC) pathogenesis. MATERIALS AND METHODS: The expression and production of CPSF4 in OSCC cell lines and tumor tissues were assessed by RT-PCR and western blot, respectively. The relationships between CPSF4 production and OSCC clinicopathological features were analyzed using immunohistochemistry. The effects of CPSF4 on viability, proliferation, migration, invasion, cell cycle distribution, and apoptosis of OSCC cells were measured by MTS assay, colony formation assay, wound-healing, transwell invasion assay, flow cytometry, and cell apoptosis assay, respectively. Western blot analysis was used to assess alteration of PI3K-AKT pathway member levels in cell lines transfected with CPSF4 siRNA. Mice xenograft models were used to determine the effect of CPSF4 on OSCC tumor growth in vivo. RESULTS: CPSF4 was highly expressed in OSCC cell lines and tumor tissues compared with adjacent normal oral tissues. High CPSF4 expression was strongly correlated with vascular invasion (P = .004), distant metastasis (P = .001), and TNM stages (P = .001). Moreover, reduction of CPSF4 levels contributed to the inhibition of cell viability, proliferation, invasion and migration, and the induction of apoptosis in OSCC cell lines. Reduction of CPSF4 levels results in OSCC cell cycle arrest in G1 phase by targeting c-Myc. CPSF4 contributed to proliferation inhibition via PI3K-AKT signaling pathway. Reduction of CPSF4 levels inhibits OSCC tumor growth in vivo. CONCLUSIONS: Our results suggest that CPSF4 supports OSCC invasion and metastasis and may be a promising therapeutic target for OSCC.

Preparation, characterization, stability, and controlled release of chitosan-coated zein/shellac nanoparticles for the delivery of quercetin.

Quercetin, an essential flavonoid compound, exhibits diverse biological activities including anti-inflammatory and antioxidant effects. Nevertheless, due to its inadequate solubility in water and vulnerability to degradation, pure quercetin is constrainedly utilized in pharmaceutical formulations and functional foods. Considering the existing scarcity of nanoparticles consisted of zein and hydrophobic biopolymers, this study developed a quercetin-loaded nanoencapsulation based on zein, shellac, and chitosan (QZSC). When the mass ratio of zein to chitosan was 4:1, the encapsulation efficiency of QZSC reached 74.95%. The ability of QZSC for scavenging DPPH radicals and ABTS radicals increased from 59.2% to 75.4% and from 47.0% to 70.2%, respectively, compared to Quercetin. For QZSC, the maximum release amount of quercetin reached 59.62% in simulated gastric fluid and 81.64% in simulated intestinal fluid, achieving controlled and regulated release in vitro. In summary, this study offers a highly promising encapsulation strategy for hydrophobic bioactive substances that are prone to instability.

Photothermal and Photocatalytic Glycol Chitosan and Polydopamine-Grafted Oxygen Vacancy Bismuth Oxyiodide (BiO1-x I) Nanoparticles for the Diagnosis and Targeted Therapy of Diabetic Wounds.

Treatment of diabetic wounds is a significant clinical challenge due to the massive infections caused by bacteria. In this study, multifunctional glycol chitosan and polydopamine-coated BiO1-x I (GPBO) nanoparticles (NPs) with near-infrared (NIR) photothermal and photocatalytic abilities are prepared. When infection occurs, the local microenvironment becomes acidic, and the pH-switchable GPBO can target the bacteria of the wound site. The NIR-assisted GPBO treatment exhibits anti-bacterial effects with fast response, high efficiency, and long duration to Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. GPBO achieves excellent photothermal imaging and CT imaging of the mouse subcutaneous abscess model. With the assistance of NIR irradiation, the GPBO promotes the healing of the diabetic wound model with the effects of anti-bacteria, anti-inflammation, the M2 polarization promotion of macrophages, and angiogenesis. This is the first-time report of nano-sized BiO1-x I. The synthesis and selected application for the imaging and targeted therapy of diabetic wounds are presented. This study offers an example of the NP-assisted precise diagnosis and therapy of bacterial infection diseases.

An Ultrasmall Cu/Cu2O Nanoparticle-Based Diselenide-Bridged Nanoplatform Mediating Reactive Oxygen Species Scavenging and Neuronal Membrane Enhancement for Targeted Therapy of Ischemic Stroke.

Ischemic stroke is one of the major causes of death and disability worldwide, and an effective and timely treatment of ischemic stroke has been a challenge because of the narrow therapeutic window and the poor affinity with thrombus of the thrombolytic agent. In this study, rPZDCu, a multifunctional nanoparticle (NP) with the effects of thrombolysis, reactive oxygen species (ROS) scavenging, and neuroprotection, was synthesized based on an ultrasmall Cu4.6O NP, the thrombolytic agent rt-PA, and docosahexaenoic acid (DHA), which is a major component of the neuronal membrane. rPZDCu showed strong thrombus-targeting ability, which was achieved by the platelet cell membrane coating on the NP surface, and a good thrombolytic effect in both the common carotid artery clot model and embolic middle cerebral artery occlusion (MCAO) model of rats. Furthermore, rPZDCu exhibited a good escape from the phagocytosis of macrophages, effective promotion of the polarization of microglia, and efficient recovery of neurobiological and behavioral functions in the embolic MCAO model of rats. This is a heuristic report of (1) the Cu0/Cu+ NP for the treatments of brain diseases, (2) the integration of DHA and ROS scavengers for central nervous system therapies, and (3) diselenide-based ROS-responsive NPs for ischemic stroke treatments. This study also offers an example of cell membrane-camouflaged stimuli-responsive nanomedicine for brain-targeting drug delivery.

An Antisense Oligonucleotide-Loaded Blood-Brain Barrier Penetrable Nanoparticle Mediating Recruitment of Endogenous Neural Stem Cells for the Treatment of Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative disease characterized by the death of dopaminergic (DA) neurons and currently cannot be cured. One selected antisense oligonucleotide (ASO) is reported to be effective for the treatment of PD. However, ASO is usually intrathecally administered by lumbar puncture into the cerebral spinal fluid, through which the risks of highly invasive neurosurgery are the major concerns. In this study, ZAAM, an ASO-loaded, aptamer Apt 19S-conjugated, neural stem cell membrane (NSCM)-coated nanoparticle (NP), was developed for the targeted treatment of PD. NSCM facilitated the blood-brain barrier (BBB) penetration of NPs, and both NSCM and Apt 19S promoted the recruitment of the neural stem cells (NSCs) toward the PD site for DA neuron regeneration. The behavioral tests demonstrated that ZAAM highly improved the efficacy of ASO on PD by the targeted delivery of ASO and the recruitment of NSCs. This work is a heuristic report of (1) nonchemoattractant induced endogenous NSC recruitment, (2) NSCM-coated nanoparticles for the treatment of neurodegenerative diseases, and (3) systemic delivery of ASO for the treatment of PD. These findings provide insights into the development of biomimetic BBB penetrable drug carriers for precise diagnosis and therapy of central nervous system diseases.

Multi-functional pH-sensitive active and intelligent packaging based on highly cross-linked zein for the monitoring of pork freshness.

Intelligent packaging not only protects food from environmental hazards but intuitively monitors the changes of food quality and safety. A novel intelligent packaging film with pH sensitivity and antibacterial and antioxidant effects was developed based on the highly cross-linked zein. The composite film with 0.05 g/g crosslinking agent had the best mechanical properties. The tensile strength (TS) and elongation-at-break (EBA) were 2.42 and 1.53 times of that of zein film, respectively. Moreover, the intelligent packaging showed longstanding antimicrobial and antioxidant effects because of the addition of the tea tree essential oil (TTEO)-loaded mesoporous silica nanoparticles (MSNs). The blueberry anthocyanin as colorimetric indicator was added in the packaging film to monitor the safety of meat products using a mobile phone. The color of the composite film as the packaging of the pork products changed from colorless to brown after 9-day storage to show the spoilage of the pork. To the best of our knowledge, this is the first-time report of 1) the application of TTEO-loaded MSNs for food packing, 2) the addition of TTEO as the antimicrobial agent for zein film, and 3) using the applications of mobile phone to measure the RBG value of the zein-based film. This study offers an example of the highly promising biodegradable intelligent packaging with multi-functions for the enhancement of food safety.

Eugenol embedded zein and poly(lactic acid) film as active food packaging: Formation, characterization, and antimicrobial effects.

Biodegradable packaging is more eco-friendly compared with the synthetic plastics. To improve the physical properties of the zein films, poly(lactic acid) (PLA) was mixed with zein to make a biodegradable blend film. The composition of the film with the best properties was the one with zein and PLA in the mass ratio of 1:1 with the addition of 20% poly(ethylene glycol) as the plasticizer. The incorporation of PLA significantly increased the elongation, reduced the tensile strength, and decreased the water vapor and gas permeabilities of zein films. The antimicrobial agent eugenol added in the film significantly inhibited the growth of both S. aureus and E. coli. The migration tests were conducted to confirm the safety of the blend films. This is the first-time report of zein-PLA blend film. The antimicrobial zein-PLA-eugenol film with enhanced mechanical and barrier properties has a high potential as active biodegradable food packaging.

Single-layer and double-layer zein-gum arabic nanoencapsulations: Preparation, structural characterization, thermal properties, and controlled release in the gastrointestinal tract.

Encapsulation is one of the most convenient ways to increase the solubility of hydrophobic compounds and enhance the protection of sensitive compounds. The development of natural and edible encapsulation systems is a challenge for the food industry. This study explored two kinds of nanoparticles (NPs) made by zein and gum arabic (GA) and investigated the protective and controlled release effect of the formed NPs on rutin. Single-layer NPs (ZG) formed with a zein and GA mixture and double-layer NPs (ZWG) with one inner layer of zein and one outer layer of GA were prepared with a series of mass ratios of zein to GA. The particle size, polydispersity index, and zeta potential were obtained, and the structure and morphology of the NPs were observed using scanning electron microscopy. As shown by the differential scanning calorimeter and thermogravimetric analysis, the heat resistance of ZG is higher than the heat resistance of ZWG. ZG showed slower release of rutin in the simulated gastric and small intestinal solutions than ZWG. These results will help in understanding the different behaviors of protection and controlled release of layered NPs made by mixtures of biopolymers, which can be directly applied to the design of delivery systems of sensitive bioactive compounds in the food industry.