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.

Boron-Containing MOF Nanoparticles with Stable Metabolism in U87-MG Cells Combining Microdosimetry To Evaluate Relative Biological Effectiveness of Boron Neutron Capture Therapy.

Accurate prediction of the relative biological effectiveness (RBE) of boron neutron capture therapy (BNCT) is challenging. The therapy is different from other radiotherapy; the dynamic distribution of boron-containing compounds in tumor cells affects the therapeutic outcome considerably and hampers accurate measurement of the neutron-absorbed dose. Herein, we used boron-containing metal-organic framework nanoparticles (BMOFs) with high boron content to target U87-MG cells and maintain the concentration of the 10B isotope in cells. The content of boron in the cells could maintain 90% (60 ppm) within 20 min compared with that at the beginning; therefore, the accurate RBE of BNCT can be acquired. The effects of BNCT upon cells after neutron irradiation were observed, and the neutron-absorbed dose was obtained by Monte Carlo simulations. The RBE of BMOFs was 6.78, which was 4.1-fold higher than that of a small-molecule boron-containing agent (boric acid). The energy spectrum of various particles was analyzed by Monte Carlo simulations, and the RBE was verified theoretically. Our results suggested that the use of nanoparticle-based boron carriers in BNCT may have many advantages and that maintaining a stable boron distribution within cells may significantly improve the efficiency of BNCT.

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.

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 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.

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.

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.

Oral Administration of Omega-3 Fatty Acids Attenuates Lung Injury Caused by PM2.5 Respiratory Inhalation Simply and Feasibly In Vivo.

For developing an effective interventional approach and treatment modality for PM2.5, the effects of omega-3 fatty acids on alleviating inflammation and attenuating lung injury induced by inhalation exposure of PM2.5 were assessed in murine models. We found that daily oral administration of the active components of omega-3 fatty acids, docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA) effectively alleviated lung parenchymal lesions, restored normal inflammatory cytokine levels and oxidative stress levels in treating mice exposed to PM2.5 (20 mg/kg) every 3 days for 5 times over a 14-day period. Especially, CT images and the pathological analysis suggested protective effects of DHA and EPA on lung injury. The key molecular mechanism is that DHA and EPA can inhibit the entry and deposition of PM2.5, and block the PM2.5-mediated cytotoxicity, oxidative stress, and inflammation.

Evaluation of Nano-Particulate-Matter-Induced Lung Injury in Mice Using Quantitative Micro-Computed Tomography.

Nano-particulate matters (NPM) induced the lung injury in mice were evaluated using quantitative micro-computed tomography in the present article. It is an important negative effect of health problems that NPM exposure provokes changes in the lung injury. The micro-computed tomography (CT) to assess lung injury in mouse models has been investigated. The dynamic structural changes in a NPM-induced lung injury mouse mode were monitored. Adults female BALB/C mice were repeatedly exposed to NPM, and micro-CT scans were performed at day 0, 3, 5 and 9. Lung samples were also collected for histological analysis at each time point. The total lung volume, the injured lung volume, and the normal lung volume were defined and calculated volume during the phase of NPM-exposure on the mice. The total and injured lung volumes of NPM-exposed mice were significantly larger than those of the mice at day 5 and 9. The data from micro-CT was consistent with alveolar enlargement and destruction by histological quantification from pathological section. The study for NPM-induced lung injury model by micro-CT may extend our understanding of the distinct pathophysiology of NPM induced lung injury in mice.

The Aggregation Induced Emission Probe of Detecting Enhanced Permeation and Retention Effects is Structured for Evaluating the Applicability of Nanotherapy to Different Tumor Individuals.

Enhanced permeation and retention (EPR) effect, the mechanism by which nanodrugs accumulate in tumors and acquire superior curative effect. The questions of these mechanisms occur because of limited clinical transformation of engineered nanomaterials after 30 years. The difference of EPR limits the therapeutic effect of nanodrugs in the individual patient. Evaluation of the EPR effect in the individual patient will aid in selecting patients who will accumulate higher amounts of nanotherapeutics and show better therapeutic efficacy. Based on varied TIMP1/MMP-9 in serum, an aggregation-induced emission luminogen probe was designed and constructed to detect and evaluate the EPR effect in model mouse. The result showed that the ratio of TIMP1/MMP-9 (in the range 0.2-1.2) and fluorescence intensity of the probe were negative linear correlation and the effects of BSA-rhodamine accumulation in tumor were individualized differences as well as correlated with the relative ratio of TIMP-1/MMP-9 in serum. Our data support the development of these biomarkers probes based on the personalized nanotherapy of tumor.

Fullerenol Nanoparticles Eradicate Helicobacter pylori via pH-Responsive Peroxidase Activity.

Helicobacter pylori (H. pylori) eradication by antibiotics and proton pump inhibitor treatment is limited by the low pH microenvironment in the stomach and can lead to antibiotic resistance. We fabricated fullerenol nanoparticles (FNPs) with varied chemical structures responding to a pinacol rearrangement of vicinal hydroxyl to form carbonyls in low pH environments. An obvious increase in C═O/C-O was induced in low pH and was positively correlated with a peroxidase-like activity. The FNPs exerted an excellent effect on H. pylori eradication in vitro and in vivo because of their peroxidase-like activity. FNP treatment of a H. pylori biofilm revealed that FNPs broke down polysaccharides in cell wall components, resulting in collapse of the bacteria. The cycles of FNPs combining and dissociating with the peroxidase substrate were detected by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and confirmed that FNPs enhance peroxidase-like activity. Further, the isothermal titration calorimetry results showed that FNPs with more C═O/C-O had greater affinity to bind the peroxidase substrates. Therefore, we suggest that varied C═O/C-O serves as a switch to respond to low pH in the stomach to kill H. pylori by inducing a peroxidase-like activity. FNPs can also overcome the challenge of antibiotic resistance to achieve H. pylori eradication in the stomach.

Intrinsic Biotaxi Solution Based on Blood Cell Membrane Cloaking Enables Fullerenol Thrombolysis In Vivo.

We report the construction of blood cell membrane cloaked mesoporous silica nanoparticles for delivery of nanoparticles [fullerenols (Fols)] with fibrinolysis activity which endows the active Fol with successful thrombolysis effect in vivo. In vitro, Fols present excellent fibrinolysis activity, and the Fol with the best fibrinolysis activity is screened based on the correlation between Fols' structure and their fibrinolysis activity. However, the thrombolytic effect in vivo is not satisfactory. To rectify the unsatisfactory situation and avoid the exogenous stimuli, a natural blood cell membrane cloaking strategy with loading the active Fol is chosen to explore as a novel thrombolysis drug. After cloaking, the therapeutic platform prolongs blood circulation time and enhances the targeting effect. Interestingly, compared with platelet membrane cloaking, red blood cell (RBC) membrane cloaking demonstrates stronger affinity with fibrin and more enrichment at the thrombus site. The Fol with RBC cloaking shows quick and efficient thrombolysis efficacy in vivo with less bleeding risk, more excellent blood compatibility, and better biosafety when compared with the clinical drug urokinase (UK). These findings not only validate the blood cell membrane cloaking strategy as an effective platform for Fol delivery on thrombolysis treatment, but also hold a great promising solution for other active nanoparticle deliveries in vivo.