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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY · 2018 · IF 3.412

Zein-Paclitaxel Prodrug Nanoparticles for Redox-Triggered Drug Delivery and Enhanced Therapeutic Efficiency

Heting Hou,Dong Zhang,Jiewen Lin,Yingying Zhang,Chengyong Li,Zhe Wang,Jiaoyan Ren,Maojin Yao,Ka-hing Wong,Yi Wang

Prodrug, in which the inactive parent drug with good bioavailability is metabolized into an active drug in the body, is one of the main strategies to target the disease site to improve the drug efficiency and reduce the adverse effects of chemotherapy. Because of the good capability of chemical modification, zein, a plant derived protein, and drugs can be conjugated through environmentally sensitive links to form prodrugs capable of triggered drug release. In this study, a novel prodrug was synthesized using paclitaxel (PTX), zein, and a disulfide linker, and nanoparticles were formed by self-assembly of the prodrug. An effective in vitro triggered release, 80–90% in 5 min, of the prodrug based nanoparticles (zein-S-S-PTX_NP) was successfully approached. The cytotoxicity of zein-S-S-PTX_NP as well as the zein encapsulation of PTX (zein_PTX_NP) and pure PTX on HeLa cells and NIH/3T3 fibroblast cells was tested using MTS assay. It showed that, after the treatment of zein-S-S-PTX_NP at the equivalent PTX concentrations of 0.1, 0.5, 1, and 5 μg/mL, respectively, zein-S-S-PTX_NP had zero damage to normal cells but a similar cytotoxicity to cancer cells as pure PTX. In the animal study, the tumor was 50% of the original size after the treatment of zein-S-S-PTX_NP for 9 days with 3 doses. This study suggested that the novel prodrug based nanoparticle zein-S-S-PTX_NP could be a promising approach in chemotherapy with targeted delivery, improved efficacy, and reduced side effects.

研究领域: 药物化学 · 生物医学工程 · 肿瘤学
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Nanomedicine-Nanotechnology Biology and Medicine · 2026 · IF 4.3

Dual-targeting zein janus nanoparticles reprogram tumor-associated macrophages for enhanced glioblastoma therapy

Kun Ma,Zicheng Liu,Senchao Chai,Qingxian Fang,Ruifan Xu,Wenrong Zhu,Yu Liu,Tong Zhang,Zhaoming Guo,Changhao Cui,Jianqiang Xu,Shigang Guo,Yang Chen

Glioblastoma (GBM) is one of the most malignant and lethal primary brain tumors, and the blood-brain barrier (BBB) poses a significant challenge to its treatment. In this study, disulfiram-loaded Zein Janus nanoparticles (Lf/M2pep@ZEN-DSF) were developed using the Pickering emulsion method for enhanced GBM therapy. Lactoferrin (Lf) was modified to one side of the Janus nanoparticles to facilitate BBB penetration and GBM targeting, while M2pep peptides were modified to the opposite side for targeting tumor-associated macrophages (TAMs). The results demonstrated that Lf/M2pep@ZEN-DSF effectively crossed the BBB and targeted brain tissues. Additionally, the Janus nanoparticles selectively targeted M2-polarized TAMs via M2pep and repolarized them into the M1 subtype for GBM therapy. Furthermore, the Janus nanoparticles significantly enhanced intracellular reactive oxygen species (ROS) generation in GBM cells. In vivo studies confirmed that the nanoparticles significantly increased drug accumulation in the brain and prolonged the survival of GBM-bearing mice. Immunohistochemical analysis revealed that Lf/M2pep@ZEN-DSF treatment induced M2-to-M1 TAM repolarization, effectively remodeling the tumor immune microenvironment. These findings collectively indicate that Lf/M2pep@ZEN-DSF is a promising nanomedicine with favorable biosafety for enhanced GBM treatment.

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LWT-FOOD SCIENCE AND TECHNOLOGY · 2024 · IF 6

Ternary nanoparticles of sodium caseinate-zein-hexaglycerol monooleate: Fabrication, characterization, and curcumin encapsulation

Xinyu Zhang,Yingxue Cheng,Hong Lin,Hailong Zhang,Weinong Zhang,Junbo He

To overcome the instability of sodium caseinate (NaCas) and zein binary nanoparticles in gastric digestion, and to improve the encapsulation of curcumin (Cur), hexaglycerol monooleate (HGMO) was employed as an anti-pepsin component to form ternary nanoparticles. The NaCas-Zein-HGMO nanoparticles were prepared using a self-assembly method that only required mixing at room temperature, and the optimal mass ratio for the components was determined to be 2:2:1. At a mass ratio of 1:20 between curcumin and zein, the NaCas-Zein-HGMO nanoparticles showed high encapsulation efficiency (91.18%) and provided effective chemical protection for curcumin. The Cur-NaCas-Zein-HGMO nanoparticles exhibited nanoscale dispersion, with a particle size about 236 nm, and demonstrated remarkable stability. In addition, the Cur-NaCas-Zein-HGMO nanoparticles exhibited improved resistance to simulated gastric fluid (SGF) digestion, increased antioxidant activity, sustained release profile, and exceptional rehydration capability. The results clearly showed that HGMO plays a crucial role in improving the physicochemical properties and encapsulation of curcumin of NaCas-Zein-HGMO nanoparticle. Hence, the novel ternary nanoparticles, NaCas-Zein-HGMO, have the potential to serve as an excellent delivery carrier for hydrophobic bioactive compounds, thereby mitigating their susceptibility to degradation by gastric digestion.

研究领域: 食品科学 · 材料科学 · 生物化学
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Innovative Food Science & Emerging Technologies · 2025 · IF 6.8

Self-assembly of Zein-based nanoparticles for oral isoliquiritigenin delivery against Salmonella infections

Cang Li,Yu Huang,Yuchen Liu,Zhipeng Li,Yao Deng,Hao Ren,Donghao Zhao,Lu Han,Jian Sun

Isoliquiritigenin (ISL) exhibits anti-inflammatory and antibacterial properties, but its application is limited by poor solubility and low bioavailability. To address this limitation, we developed ISL-encapsulated nanoparticles (ISL@NPs) using self-assembling Zein protein and hydrophilic Gum Arabic to load ISL. Under optimized conditions (Zein/GA ratio of 1:1, Zein content of 200 mg, pH 4), the fabricated ISL@NPs exhibited smaller particle size and robust stability. The aqueous solubility of ISL was significantly enhanced from 5.11 μg/mL to over 400 μg/mL upon encapsulation into ISL@NPs. Additionally, ISL@NPs alleviated the thermal degradation of ISL under high-temperature conditions and demonstrated rapid drug release in simulated inflammatory environments. Animal experiment results showed that ISL@NPs significantly enhanced the bioavailability of ISL and provided exceptional therapeutic efficacy against Salmonella infection. In summary, this study developed stable and effective ISL@NPs using food-derived materials, offering a novel antibiotic alternative for Salmonella control.

研究领域: 纳米技术 · 药学 · 食品科学 · 生物医学工程 · 微生物学 · 药物递送系统
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ACS Food Science & Technology · 2021 · IF 0

Studies on the Molecular Interactions between Plant-Derived Protein Zein and Small Molecules

Yajing Wang,Fangzhi Cao,Mingchen Ge,Shiqun Lv,Jun Gao

Zein, a kind of plant-derived natural polymer, has a unique self-assembly behavior due to its unique structure and is an ideal material for the preparation of nanocarriers. The present study aims at detecting molecular interactions and affinity between zein and small molecules with different polarities by employing UV spectroscopy, dynamic laser light scattering, and fluorescence spectroscopy to provide some reference for the development and utilization of zein-based nanocarriers. The ethanol concentration dependent solubility and UV spectra were confirmed and compared. The hydrodynamic diameter, ζ potential, and productivity of resultant nanoparticles were comprehensively collected to evaluate the self-assembly behaviors of zein. The fluorescence correlation spectroscopy and thermodynamic principle were used to analyze the noncovalent interaction between zein and small molecules. The main driving force between hydrophobic 8-anilinonaphthalene-1-sulfonic acid (ANS) and zein is hydrophobic force, while those with hydrophilic rhodamine B are hydrogen bonds and van der Waals forces.

研究领域: 植物生物化学 · 纳米技术 · 高分子科学 · 分子相互作用 · 药物递送系统
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INTERNATIONAL JOURNAL OF FOOD SCIENCE AND TECHNOLOGY · 2019 ·Vol. 55 ·期 5 ·1924-1934 · IF 2.281

Antioxidant Pickering emulsions stabilised by zein/tannic acid colloidal particles with low concentration

Bin Zhou,Sihai Gao,Xiuting Li,Hongshan Liang,Shugang Li

Summary Pickering emulsions are widely used as a carrier and protective systems in many fields for encapsulation-specific bioactive substances. In this current study, we fabricated an antioxidant Pickering emulsions stabilised by zein/tannic acid nanoparticle. Results showed that coalescence and creaming stability of the emulsion highly depended on the concentration of the particles and the zein to TA ratio in the formulation. A 0.3% concentration of zein and a 1:1 zein to TA ratio was found to exhibit optimal stabilising capability. Given the intrinsic antioxidant activity of tannic acid, which forms a protective shell, the oxidative deterioration of the oil in the emulsion could be significantly prevented. These data suggest that the ZTNPs established in the present study are a promising emulsifier in the Pickering emulsion. It is promising as a green, safe, high-performance particle stabiliser and a novel food ingredient for use in interface-oriented food systems.

CAS / MDL: 1401-55-4
研究领域: 食品科学 · 材料科学
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INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH · 2018 · IF 3.141

Self-Assembly of Zein-Based Microcarrier System for Colon-Targeted Oral Drug Delivery

Hongdi Wang,Xiaotong Zhang,Wei Zhu,Yanbin Jiang,Zhibing Zhang

The advances in pharmaceutical technology allow for the development of various region-selective delivery systems for oral administration to optimize local and systemic therapy. In this paper, micronization associated with a polymorph modification approach was proposed for improving the solubility of hydrophobic drugs for developing a Zein-based colon-targeted delivery system. A microcarrier based on self-assembled structures of Zein was fabricated via a built-in ultrasonic dialysis process, which displayed high payload of a model drug, indomethacin (Indo), with its optimal crystal form. The possible self-assembly mechanism of Zein/Indo forming porous structure in the ultrasonic dialysis process was attributed to the results of intra- and/or intermolecular interactions between Zein and Indo. The designed microspheres, Zein-Indo@PDA, with a surface coating of polydopamine (PDA) not only rendered them enhanced stability and mechanical resistance but also hindered the premature drug release at undesired sites. This innovative formulation design may offer better chances of colon-targeted release.

CAS / MDL: 62-31-7
研究领域: 药剂学 · 生物医学工程
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Materials Science & Engineering C-Materials for Biological Applications · 2017 · IF 4.164

Electrospun water-stable zein/ethyl cellulose composite nanofiber and its drug release properties

Hangyi Lu,Qingqing Wang,Guohui Li,Yuyu Qiu,Qufu Wei

A simple and cost-effective way to prepare water-stable zein-based nanofibers for potential drug delivery was presented in this article. Corn protein zein was co-electrospun with hydrophobic ethyl cellulose. Indomethacin, as a model drug, was incorporated in situ into the composite nanofibers. Scanning electron microscopy and element mapping revealed the morphologies of drug-loaded nanofibers and drug distribution, respectively. Fourier transform infrared spectra confirmed the physical blending among the components. Differential scanning calorimetry and X-ray diffraction demonstrated the physical state of drug and polymers in the nanofiber matrix. The composite nanofibers showed a sustained diffusion-controlled release according to the results of in vitro dissolution tests.

研究领域: 材料科学 · 药剂学 · 生物医学工程
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JOURNAL OF MOLECULAR LIQUIDS · 2021 · IF 6.165

Interaction mechanism of phenolic acids and zein: A spectrofluorometric and molecular dynamics investigation

Yuandong Yu,Guizhao Liang

Zein, a mixture protein existed in maize endosperm, has desirable biocompatibility and bioadhesion, which has been extensively applied as carrier materials in food and pharmaceutical industry. However, to the best of our knowledge, there is no published paper that has systematically explored the binding between phenolic acids and zein on the basis of the regression model. In this study, we investigated interaction behaviors of 19 phenolic acids with zein via fluorescence spectroscopy and partial least squares regression (PLS) modeling, among which trans -ferulic acid (hydroxycinnamic acid with the highest pK A values) and 3,5-dinitrosalicylic acid (hydroxybenzoic acid with the lowest pK A values) were selected to further investigate their interaction mechanisms based on molecular modeling methods. The fluorescence spectra results showed that these 19 phenolic acids can cause obvious fluorescence quenching of zein, and the binding capacities of hydroxycinnamic acid were generally better than those of hydroxybenzoic acid. Molecular modeling results exhibited that the hydrogen bonding interaction and van der Waal force played crucial roles in maintaining the stable binding of these complexes; the formation of hydrogen bonds between Tyr-192 and carboxyl group on hydroxycinnamic acid was suggested to be the critical interaction causing stronger fluorescence quenching. The PLS modeling revealed that molecular descriptors P1s, Ks, ASP, Km, L/BW, P1m, JGI7, P1e, P1v, X3A had positive effects to the pK A of 19 phenolic acids, while P2s, P2m, L2s, PW4, JGI3 had negative effects. These findings suggest that zein should have the potential application as the polyphenol delivery system, and provide information for engineering zein to become more efficiently polyphenol carriers.

研究领域: 食品科学 · 生物化学 · 药物化学
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Food Science and Technology · 2022 · IF 2.602

Effect of sodium trimetaphosphate modification on the structure and rheological properties of zein

ZHANG Hao,ZHAO Yanyan,KANG Xiaofeng,LI Hongbo,MO Haizhen

The modification of zein with sodium trimetaphosphate (STMP) as a cross-linking agent was studied. The effects of the mass ratio of STMP to zein (RS/Z), pH, reaction temperature and time on the rheological properties of modified zein solution (Z-SP) were evaluated. By using response surface methodology, the optimal modification conditions were also determined as following: RS/Z 0.03, pH 6.8, reaction time 2 h, reaction temperature 25 °C. Under these conditions, the observed shear stress of Z-SP solution was 35.0025 Pa, close to the predicted value. Compared with natural zein, the viscosity of Z-SP increased with the increasing shear rate, which was attributed to the structural changes, as evidenced by circular dichroism (CD) and Fourier transform infrared (FT-IR) analysis.

CAS / MDL: 9010-66-6
研究领域: 食品科学 · 生物化学
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JOURNAL OF PHARMACEUTICAL SCIENCES · 2023 · IF 3.8

Fabrication of Luteolin Loaded Zein-Caseinate Nanoparticles and its Bioavailability Enhancement in Rats

Qiao-Ting Xu,Wen-Xuan Zhang,Hai-Xia Xu,Qing-Feng Zhang

Luteolin loaded zein nanoparticles (Lut-ZNP) were prepared by using sodium caseinate as an electrostatic stabilizer. The formulation of the nanoparticles was optimized. Lut-ZNP were spray-dried, and the physicochemical properties were characterized by SEM, XRD , FT-IR and DSC. Then, the bioavailability of luteolin in rats was determined. Under the formulation of luteolin, zein and sodium caseinate with mass ratio of 1:5:15, the particle size, ζ-potential, encapsulation efficiency and loading efficiency of Lut-ZNP were 171.8 nm , -49.05 mV, 85.85% and 3.15%, respectively. Luteolin existed in the nanoparticles with amorphous form. Lut-ZNP exhibited good redispersibility in water after drying. Compared with free luteolin, the solubility, stability and release of luteolin in Lut-ZNP were greatly improved. Besides, the fecal excretion of luteolin in rats was significantly reduced after oral administration of Lut-ZNP. In addition to native luteolin, its metabolites including sulfate, glucuronidate and methylated glucuronidate were found in rat plasma. Lut-ZNP significantly increased the plasma concentrations of luteolin and its metabolites, and the bioavailability of luteolin was enhanced by 2.92 times.

CAS / MDL: 491-70-3
研究领域: 药剂学 · 纳米技术 · 药物递送系统 · 药代动力学
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JOURNAL OF FOOD ENGINEERING · 2022 · IF 6.203

Fabrication of zein–carboxymethyl cellulose nanoparticles for co-delivery of quercetin and resveratrol

Zhongyu Yang,David Julian McClements,Xinwen Peng,Zhenlin Xu,Man Meng,Long Chen,Zhengyu Jin

Composite nanoparticles composed of zein and carboxymethyl cellulose (CMC) designed for the co-delivery of resveratrol and quercetin were prepared using antisolvent precipitation. At a mass ratio of zein-to-CMC of 2:1, composite nanoparticles with small average diameters (217 nm) could be formed. These nanoparticles had good thermal stability and did not aggregate or sediment when stored at pH 3.0–6.0. Encapsulation of quercetin and resveratrol simultaneously within the composite nanoparticles significantly improved their antioxidant activities . This study suggests that composite nanoparticles may have good physical and chemical stability, which may increase their application as co-delivery systems for bioactive components. As a result, they may be useful for personalized nutritional applications where combinations of bioactive compounds need to be orally administered.

CAS / MDL: 501-36-0
研究领域: 纳米技术 · 药学 · 食品科学 · 生物技术
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