Advanced ethylene-absorbing and cushioning depending on the 3D porous-structured fruit packaging: Toward polyurethane foam manipulation using zein and soybean oil polyol substrates.

Fruits are essential sources of nutrients in our daily diet; however, their spoilage is often intensified by mechanical damage and the ethylene phytohormone, resulting in significant economic losses and exacerbating hunger issues. To address these challenges, this study presented a straightforward in situ synthesis protocol for producing Z/SOPPU foam, a 3D porous-structured fruit packaging. This innovative packaging material offered advanced ethylene-adsorbing and cushioning capabilities achieved through stirring, heating, and standing treatments. The results demonstrated that the Z/SOPPU foam, with its porous structure, served as an excellent packaging material for fruits, maintaining the intact appearance of tomatoes even after being thrown 72 times from a height of 1.5 m. Additionally, it exhibited desirable hydrophobicity (contact angle of 114.31 ± 0.82°), degradability (2.73 ± 0.88 % per 4 weeks), and efficient ethylene adsorption (adsorption rate of 13.2 ± 1.7 mg/m3/h). These remarkable characteristics could be attributed to the unique 3D micron-porous configuration, consisting of soybean oil polyol polyurethane foam for mechanical strain cushioning and zein for enhanced ethylene adsorption efficiency. Overall, this research offers an effective and original approach to the rational design and fabrication of advanced bio-based fruit packaging.

Conformations of a highly expressed Z19 α-zein studied with AlphaFold2 and MD simulations.

α-zeins are amphiphilic maize seed storage proteins with material properties suitable for a multitude of applications e.g., in renewable plastics, foods, therapeutics and additive manufacturing (3D-printing). To exploit their full potential, molecular-level insights are essential. The difficulties in experimental atomic-resolution characterization of α-zeins have resulted in a diversity of published molecular models. However, deep-learning α-zein models are largely unexplored. Therefore, this work studies an AlphaFold2 (AF2) model of a highly expressed α-zein using molecular dynamics (MD) simulations. The sequence of the α-zein cZ19C2 gave a loosely packed AF2 model with 7 α-helical segments connected by turns/loops. Compact tertiary structure was limited to a C-terminal bundle of three α-helices, each showing notable agreement with a published consensus sequence. Aiming to chart possible α-zein conformations in practically relevant solvents, rather than the native solid-state, the AF2 model was subjected to MD simulations in water/ethanol mixtures with varying ethanol concentrations. Despite giving structurally diverse endpoints, the simulations showed several patterns: In water and low ethanol concentrations, the model rapidly formed compact globular structures, largely preserving the C-terminal bundle. At ≥ 50 mol% ethanol, extended conformations prevailed, consistent with previous SAXS studies. Tertiary structure was partially stabilized in water and low ethanol concentrations, but was disrupted in ≥ 50 mol% ethanol. Aggregated results indicated minor increases in helicity with ethanol concentration. ß-sheet content was consistently low (∼1%) across all conditions. Beyond structural dynamics, the rapid formation of branched α-zein aggregates in aqueous environments was highlighted. Furthermore, aqueous simulations revealed favorable interactions between the protein and the crosslinking agent glycidyl methacrylate (GMA). The proximity of GMA epoxide carbons and side chain hydroxyl oxygens simultaneously suggested accessible reactive sites in compact α-zein conformations and pre-reaction geometries for methacrylation. The findings may assist in expanding the applications of these technologically significant proteins, e.g., by guiding chemical modifications.

Layer-by-layer assembly of quercetin-loaded zein/γPGA/low-molecular-weight chitosan/fucoidan nanosystem for targeting inflamed blood vessels.

Chitosan acts as a versatile carrier in polymeric nanoparticle (NP) for diverse drug administration routes. Delivery of antioxidants, such as quercetin (Qu) showcases potent antioxidant and anti-inflammatory properties for reduction of various cardiovascular diseases, but low water solubility limits uptake. To address this, we developed a novel layer-by-layer zein/gamma-polyglutamic acid (γPGA)/low-molecular-weight chitosan (LC)/fucoidan NP for encapsulating Qu and targeting inflamed vessel endothelial cells. We used zein (Z) and γPGA (r) to encapsulate Qu (Qu-Zr NP) exhibited notably higher encapsulation efficiency compared to zein alone. Qu-Zr NP coated with LC (Qu-ZrLC2 NP) shows a lower particle size (193.2 ± 2.9 nm), and a higher zeta potential value (35.2 ± 0.4 mV) by zeta potential and transmission electron microscopy analysis. After coating Qu-ZrLC2 NP with fucoidan, Qu-ZrLC2Fa NP presented particle size (225.16 ± 0.92 nm), zeta potential (-25.66 ± 0.51 mV) and maintained antioxidant activity. Further analysis revealed that Qu-ZrLC2Fa NP were targeted and taken up by HUVEC cells and EA.hy926 endothelial cells. Notably, we observed Qu-ZrLC2Fa NP targeting zebrafish vessels and isoproterenol-induced inflamed vessels of rat. Our layer-by-layer formulated zein/γPGA/LC/fucoidan NP show promise as a targeted delivery system for water-insoluble drugs. Qu-ZrLC2Fa NP exhibit potential as an anti-inflammatory therapeutic for blood vessels.

Electrospraying and electrospinning of tannic acid-loaded zein: Characterization and antioxidant effects in astrocyte culture exposed to E. coli lipopolysaccharide.

Tannic acid (TA) exhibits low bioavailability in the gastrointestinal tract, limiting its benefits due to small amounts reaching the CNS. Thus, the objective of this study was to develop zein capsules and fibers by electrospraying/electrospinning for encapsulation of TA. Polymeric solutions were evaluated by electrical conductivity, density, and viscosity. In zein capsules, up to 2 % TA was added, and in fibers, up to 1 % TA was added. Zein capsule and fiber with TA were evaluated by morphology, size distribution, encapsulation efficiency, thermal and thermogravimetric properties, and functional groups. Zein capsule with 1.5 % TA was evaluated in astrocyte culture for cytotoxicity and antioxidant activity. TA zein capsules and fibers exhibited high encapsulation efficiency and homogeneous morphology. TA encapsulated in zein presented higher thermal stability than free TA. TA zein capsule did not present toxicity and elicited antioxidant action in lipopolysaccharide-induced astrocyte culture. Capsules and fibers were successfully produced by electrospraying/electrospinning techniques.

Sustainable bioactive food packaging based on electrospun zein-polycaprolactone nanofibers integrated with aster yomena extract loaded halloysite nanotubes.

Compostable zein-polycaprolactone (PZ) electrospun nanofiber integrated with different concentrations of Aster yomena extract loaded halloysite nanotubes (A. yomena-HNT) as bioactive nanofibrous food packaging is reported. SEM micrographs reveal heterogeneous nanofibers. A. yomena extract used in the study showed weak antioxidant activity with AAI and TEAC values of 0.229 and 0.346. In vitro, release profile over 7 days of A. yomena indicates a controlled, sustained, and prolonged release. The prepared nanofibers were effective against both gram-positive and gram-negative bacteria. The prepared composite nanofibers were rendered biocompatible and nontoxic when subjected to WST-1 and LDH assay after incubating with NIH 3T3 mouse fibroblast cell line. PZ-15 nanofiber packaging showed the best postharvest quality preservation in Black mulberry fruits after 4 days of storage at 25 °C and 85 % Rh. Moreover, the in vitro decomposition test reveals that the fabricated nanofibers decompose in the soil and do not pose as a threat to the environment.

Metformin Loaded Zein Polymeric Nanoparticles to Augment Antitumor Activity against Ehrlich Carcinoma via Activation of AMPK Pathway: D-Optimal Design Optimization, In Vitro Characterization, and In Vivo Study.

Metformin (MET), an antidiabetic drug, is emerging as a promising anticancer agent. This study was initiated to investigate the antitumor effects and potential molecular targets of MET in mice bearing solid Ehrlich carcinoma (SEC) as a model of breast cancer (BC) and to explore the potential of zein nanoparticles (ZNs) as a carrier for improving the anticancer effect of MET. ZNs were fabricated through ethanol injection followed by probe sonication method. The optimum ZN formulation (ZN8) was spherical and contained 5 mg zein and 30 mg sodium deoxycholate with a small particle size and high entrapment efficiency percentage and zeta potential. A stability study showed that ZN8 was stable for up to three months. In vitro release profiles proved the sustained effect of ZN8 compared to the MET solution. Treatment of SEC-bearing mice with ZN8 produced a more pronounced anticancer effect which was mediated by upregulation of P53 and miRNA-543 as well as downregulation of NF-κB and miRNA-191-5p gene expression. Furthermore, ZN8 produced a marked elevation in pAMPK and caspase-3 levels as well as a significant decrease in cyclin D1, COX-2, and PGE2 levels. The acquired findings verified the potency of MET-loaded ZNs as a treatment approach for BC.

Biomaterial-based combinatorial approach of aescin-comprised zein-coated gelatin nanoparticles alleviates synovial inflammation in experimental inflammatory arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that mostly affects joints. Although RA therapy has made significant progress, difficulties including extensive medication metabolism and its quick clearance result in its inadequate bioavailability. The anti-inflammatory effect of zein was reported with other medications, but it has certain limitations. There are reports on the anti-oxidant and anti-inflammatory effect of aescin, which exhibits low bioavailability for the treatment of rheumatoid arthritis. Also, the combinatorial effect of zein with other effective drug delivery systems is still under investigation for the treatment of experimental collagen-induced rheumatoid arthritis. The focus of this study was to formulate and define the characteristics of zein-coated gelatin nanoparticles encapsulated with aescin (Ze@Aes-GNPs) and to assess and contrast the therapeutic effectiveness of Ze@Aes-GNPs towards collagen-induced RA in Wistar rats. Nanoprecipitation and the layer-by-layer coating process were used to fabricate Ze@Aes-GNPs and their hydrodynamic diameter was determined to be 182 nm. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were used to further validate the size, shape, and surface morphology of Ze@Aes-GNPs. When tested against foreskin fibroblasts (BJ), these nanoparticles demonstrated significantly high cytocompatibility. Both Aes and Ze@Aes-GNPs were effective in treating arthritis, as shown by the decreased edoema, erythema, and swelling of the joints, between which Ze@Aes-GNPs were more effective. Further, it was demonstrated that Aes and Ze@Aes-GNPs reduced the levels of oxidative stress (articular elastase, lipid peroxidation, catalase, superoxide dismutase and nitric oxide) and inflammatory indicators (TNF-α, IL-1ß and myeloperoxidase). The histopathology findings further demonstrated that Ze@Aes-GNPs considerably reduced the infiltration of inflammatory cells at the ankle joint cartilage compared to Aes. Additionally, immunohistochemistry examination showed that treatment with Ze@Aes-GNPs suppressed the expression of pro-inflammatory markers (COX-2 and IL-6) while increasing the expression of SOD1. In summary, the experiments indicated that Aes and Ze@Aes-GNPs lowered the severity of arthritis, and critically, Ze@Aes-GNPs showed better effectiveness in comparison to Aes. This suppression of oxidative stress and inflammation was likely driven by Aes and Ze@Aes-GNPs.

Improving the properties of whey protein isolate-zein nanogels with novel acidifiers: Re-dispersity, stability and quercetin bioavailability.

Low bioavailability of quercetin (Que) reduces its preclinical and clinical benefits. In order to improve Que bioavailability, a novel whey protein isolate (WPI)-zein nanogel was prepared by pH-driven self-assembly and heat-induced gelatinization. The results showed that hydrochloric acid can be substituted by both acetic acid and citric acid during the pH-driven process. After encapsulation, the bioavailability of Que in nanogels (composed of 70 % WPI) induced by different acidifiers increased to 19.89 % (citric acid), 21.65 % (hydrochloric acid) and 24.34 % (acetic acid), respectively. Comparatively, nanogels induced by acetic acid showed higher stability (pH and storage stability), re-dispersibility (75.62 %), Que bioavailability (24.34 %), and antioxidant capacity (36.78 % for DPPH scavenging rates). s improved performance of nanogels. In mechanism, acetic acid significantly balanced different intermolecular forces by weakening "acid-induced denaturation" effect. Moreover, the faster binding of Que and protein as well as higher protein molecular flexibility and randomness (higher ratio of random coil) was also observed in nanogels induced by acetic acid. All of these changes contributed to improve nanogels performances. Overall, WPI-zein nanogels induced by acetic acid might be a safe, efficiency and stable delivery system to improve the bioavailability of hydrophobic active ingredients.

Lutein encapsulation into dual-layered starch/zein gels using 3D food printing: Improved storage stability and in vitro bioaccessibility.

The ability of 3D printing to encapsulate, protect, and enhance lutein bioaccessibility was investigated under various printing conditions. A spiral-cube-shaped geometry was used to investigate the effects of printing parameters, namely zein concentration (Z; 20, 40, and 60 %) and printing speed (PS; 4, 8, 14, and 20 mm/s). Coaxial extrusion 3D printing was used with lutein-loaded zein as the internal flow material, and corn starch paste as the external flow material. The viscosities of the inks, microstructural properties, storage stability, and bioaccessibility of encapsulated lutein were determined. The sample printed with a zein concentration of 40 % at a printing speed of 14 mm/s (Z-40/PS-14) exhibited the best shape integrity. When lutein was entrapped in starch/zein gels (Z-40/PS-14), only 39 % of lutein degraded after 21 days at 25 °C, whereas 78 % degraded at the same time when crude lutein was studied. Similar improvements were also observed after storing at 50 °C for 21 days. Furthermore, after simulated digestion, the bioaccessibility of encapsulated lutein (9.8 %) was substantially higher than that of crude lutein (1.5 %). As a result, the developed delivery system using 3D printing could be an effective strategy for enhancing the chemical stability and bioaccessibility of bioactive compounds (BCs).

Oregano essential oil encapsulated in zein-pectin-chitosan nanoparticles to improve the storage quality of Harbin red sausage.

In this study, the effect of oregano essential oil loaded in zein-pectin-chitosan (Zein-PC-CS-OEO) nanoparticles on the quality of Harbin red sausage during storage was examined. Zein-PC-CS-OEO nanoparticles exhibit the better encapsulation efficiency, antioxidant and antibacterial properties than these of other prepared nanoparticles, which were subsequently incorporated into Harbin red sausage with different concentrations. The physicochemical properties, bacterial community structure, and flavor characteristics of the Harbin red sausage were determined. Both thiobarbituric acid values and the growth of dominant spoilage bacteria in Harbin red sausage are inhibited by Zein-PC-CS-OEO nanoparticles, while the total aerobic bacteria count is reduced. These results indicate that the storage quality of Harbin red sausage is improved by Zein-PC-CS-OEO nanoparticles. It is worth noting that the shelf life of Harbin red sausage supplemented with 0.1 % Zein-PC-CS-OEO nanoparticles is extended to 9 d, and the flavor characteristics of which are better maintained. This study provides a new approach to extend the application of essential oil and improve the storage quality of Harbin red sausage.

In vitro and in silico investigation of glycyrrhizic acid encapsulated zein nanoparticles: A synergistic targeted drug delivery approach for breast cancer.

This study presents an innovative approach for targeted drug delivery through the development of Glycyrrhizic acid-loaded zein nanoparticles (GA-LNPs) as a proficient carrier system. The juxtaposition of zein, a hydrophobic biological macromolecule as a protein carrier, and Glycyrrhizic acid (GA), a hydrophilic therapeutic compound, exemplifies the adaptability of hydrocolloids within cutting-edge drug delivery systems. The characterization and functional traits of research encompass multifaceted analyses of natural macromolecules, which elucidate the homogeneous and spherical morphology of GA-LNPs with an average size of 170.49 nm. The controlled drug release profile of GA, orchestrated under simulated gastrointestinal conditions, adheres to diffusion-based Higuchi kinetics, reflecting the controlled release of the natural macromolecules. The intermolecular interactions among Zein, GA, and cross-linker EDC, facilitated through molecular dynamics simulations, fortify the structural integrity of the encapsulation matrix. In Vitro studies revealed enhanced cellular uptake of GA-LNPs in MCF-7 breast cancer cells. This cellular internalization was further confirmed through cytotoxicity assessments using MTT and apoptosis assays (fluorescence microscopy), which demonstrated the prominent anticancer effects of GA-LNPs on MCF-7 in time/dose-dependent manner. The successful formulation of GA-LNPs, coupled with their sustained release and potent anticancer properties, makes them a potential platform for advanced targeted therapeutic strategies in biomedical applications.

Revolutionizing Cancer Treatment: The Promising Horizon of Zein Nanosystems.

Various nanomaterials have recently become fascinating tools in cancer diagnostic applications because of their multifunctional and inherent molecular characteristics that support efficient diagnosis and image-guided therapy. Zein nanoparticles are a protein derived from maize. It belongs to the class of prolamins possessing a spherical structure with conformational properties similar to those of conventional globular proteins like ribonuclease and insulin. Zein nanoparticles have gained massive interest over the past couple of years owing to their natural hydrophilicity, ease of functionalization, biodegradability, and biocompatibility, thereby improving oral bioavailability, nanoparticle targeting, and prolonged drug administration. Thus, zein nanoparticles are becoming a promising candidate for precision cancer drug delivery. This review highlights the clinical significance of applying zein nanosystems for cancer theragnostic─moreover, the role of zein nanosystems for cancer drug delivery, anticancer agents, and gene therapy. Finally, the difficulties and potential uses of these NPs in cancer treatment and detection are discussed. This review will pave the way for researchers to develop theranostic strategies for precision medicine utilizing zein nanosystems.

Zein nanoparticles containing ceftazidime and tobramycin: antibacterial activity against Gram-negative bacteria.

Aims: This work describes the encapsulation of ceftazidime and tobramycin in zein nanoparticles (ZNPs) and the characterization of their antibacterial and antibiofilm activities against Gram-negative bacteria. Materials & methods: ZNPs were synthesized by nanoprecipitation. Cytotoxicity was assessed by MTT assay and antibacterial and antibiofilm assays were performed by broth microdilution and violet crystal techniques. Results: ZNPs containing ceftazidime (CAZ-ZNPs) and tobramycin (TOB-ZNPs) showed drug encapsulation and thermal stability. Encapsulation of the drugs reduced their cytotoxicity 9-25-fold. Antibacterial activity, inhibition and eradication of biofilm by CAZ-ZNPs and TOB-ZNPs were observed. There was potentiation when CAZ-ZNPs and TOB-ZNPs were combined. Conclusion: CAZ-ZNPs and TOB-ZNPs present ideal physical characteristics for in vivo studies of antibacterial and antibiofilm activities.

A nanotechnology product was developed to treat diseases caused by bacteria. This prototype showed the ideal characteristics and could be administered by ingestion through the mouth, aspiration through the nose or injection into the veins. The prototype did not harm or kill human cells. It killed the bacteria and prevented the formation of a type of protection against antibiotics that bacteria can produce, called a biofilm. Nanotechnology products are a promising alternative for the treatment of bacterial infections.

Insights into the preparation of zein nanoparticles by continuous membrane nanoprecipitation.

Nanoparticles (NPs) preparation is limited to an exclusive use in batch processes and small-scale formulations. The use of membranes as high-performance micromixers is expected to open new scenarios to overcome limitations of conventional nanoprecipitation system such as stirred tank (ST) nanoprecipitation. The ability of the porous membrane to add uniformly one phase to another and govern their mixing at the membrane interface seems to be an important parameter for obtaining uniform NPs. Inorganic membranes (pore size of 1 µm) were used to carry out membrane nanoprecipitation (MN) to form Zein nanoparticles (ZNPs) at pores level by non-solvent induced phase separation. A systematic study of the preparation of ZNPs in the ST and MN systems was carried out to establish the Ouzo diagram. The influence of zein concentration and solvent to non-solvent ratio on the size and size distribution of ZNPs was also investigated. A wider stable Ouzo zone was obtained with MN than with the ST process. ZNPs size increased from 100 nm up to 700 nm, while maintaining low polydispersity index (PDI < 0.2). The results demonstrate the suitability of MN for the continuous production of ZNPs and open the possibility of scaling up the nanoprecipitation process.

Fabrication and characterization of curcumin-loaded composite nanoparticles based on high-hydrostatic-pressure-treated zein and pectin: Interaction mechanism, stability, and bioaccessibility.

We successfully designed curcumin (Cur)-loaded composite nanoparticles consisting of high-hydrostatic-pressure-treated (HHP-treated) zein and pectin with a pressure of 150 MPa (zein-150 MPa-P-Cur), showing nano-spherical structure with high zeta-potential (-36.72 ± 1.14 mV) and encapsulation efficiency (95.64 ± 1.23 %). We investigated the interaction mechanism of the components in zein-150 MPa-P-Cur using fluorescence spectroscopy, molecular dynamics simulation, Fourier-transform infrared spectrometry and scanning electron microscopy techniques. Compared with zein-P-Cur, the binding sites and binding energy (-53.68 kcal/mol vs. - 44.22 kcal/mol) of HHP-treated zein and Cur were increased. Meanwhile, the interaction force among HHP-treated zein, pectin, and Cur was significantly enhanced, which formed a tighter and more stable particle structure to further improve package performance. Additionally, Cur showed the best chemical stability in zein-150 MPa-P-Cur. And the bioavailability of Cur was increased to 65.53 ± 1.70 %. Collectively, composite nanoparticles based on HHP-treated zein and pectin could be used as a promising Cur delivery system.

Zein and tannic acid hybrid particles improving physical stability, controlled release properties, and antimicrobial activity of cinnamon essential oil loaded Pickering emulsions.

Pickering emulsion loading essential oil has demonstrated a promising strategy as delivery system in food preservation, but localization in stability and antimicrobial activity limits application. In this study, Pickering emulsions co-loaded with tannic acid and cinnamon essential oil (ZTC) have been developed based on zein and tannic acid complexes (ZT) mediated interfacial engineering. Fourier transform infrared, fluorescence spectroscopy, and molecular docking results indicated tannic acid altered the structural of zein. Interfacial tension results indicated that tannic acid accelerated the adsorbed speed of zein particles by decreased interfacial tension (11.99-9.96 mN/m). ZT5 formed a viscoelastic and dense layer in oil-water interface than that for other ZTs, which improved stability and control release performance of ZTC. Furthermore, the ZTC showed an effective antimicrobial activity against spoilage organisms Pseudomonad paralactis MN10 and Lactobacillus sakei VMR17. These findings provide new insight for developing co-loaded multiple antimicrobial agents within Pickering emulsion as a delivery system.

The pro-absorptive effect of glycosylated zein-fatty acid complexes on fucoxanthin via the lipid transporter protein delivery pathway.

Growing research confirms that lipid transport proteins play a key role in the trans-intestinal epithelial transport of carotenoids. In this study, to simultaneously improve the digestive stability and intestinal absorption of fucoxanthin (FX), functionalized vectors with a capability of up-regulating the expression of FX-specific lipid transporter proteins was fabricated. The results showed that myristic acid, palmitic acid, and stearic acid effectively promoted FX-specific lipid transporter protein expression and formed stable self-assembly complexes with Millard-modified zein (MZ). The FX was sufficiently encapsulated in the MZ-fatty acid (FA) particles, forming spherical nanoparticles with a "core-shell" structure. Simulated gastrointestinal digestion showed that FA introduction significantly increased the FX bioaccessibility. In vivo results further verified that adding FAs dramatically increased the FX serum response concentration. These findings suggest that incorporating nutrients that can promote lipid transporter protein expression into delivery vehicles should be an effective strategy for improving oral carotenoid absorption.

Vitexin-rhamnoside encapsulated with zein-pectin nanoparticles relieved high-fat diet induced lipid metabolism disorders in mice by altering the gut microbiota.

This study aimed to investigate the modulatory effects of Vitexin-rhamnoside (VR) and Zein-VR-pectin nanoparticles (VRN) on lipid metabolism disorders induced by high-fat diet (HFD). The ingestion of VR or VRN attenuated dyslipidemia and fat accumulation in HFD mice, and improved intestinal dysbiosis by regulating the relative abundance of dominant bacteria, alleviating chronic inflammation and hepatic injury in HFD mice. The intervention effect of VRN was significantly higher than that of VR. After fecal microbiota transplantation (FMT) treatment, the fecal microbiota of VRN-treated donor mice significantly attenuated the symptoms associated with hyperlipidemia, confirming that VRN ameliorates HFD-induced disorders of lipid metabolism by modulating the gut microbiota, especially increasing the abundance of Rombousia and Faecalibaculum. Overall, VRN can regulate the gut microbiota and thus improve lipid metabolism. The present study provided new evidence that nanoparticles enhance the bioavailability of food bioactive ingredients.

Co-delivery of siAEG-1 and doxorubicin to treat osteosarcoma via nanomicelles for azide-alkyne "click" conjugation of poly(l-lysine) dendrons onto Zein.

Astrocyte elevated gene-1 (AEG-1) oncogene is a notorious and evolving target in a variety of human malignancies including osteosarcoma. The RNA interference (RNAi) has been clinically proven to effectively knock down specific genes. To successfully implement RNAi in vivo, protective vectors are required not only to protect unstable siRNAs from degradation, but also to deliver siRNAs to target cells with controlled release. Here, we synthesized a Zein-poly(l-lysine) dendrons non-viral modular system that enables efficient siRNA-targeted AEG-1 gene silencing in osteosarcoma and encapsulation of antitumor drugs for controlled release. The rational design of the ZDP integrates the non-ionic and low immunogenicity of Zein and the positive charge of the poly(l-lysine) dendrons (DPLL) to encapsulate siRNA and doxorubicin (DOX) payloads via electrostatic complexes and achieve pH-controlled release in a lysosomal acidic microenvironment. Nanocomplexes-directed delivery greatly improves siRNA stability, uptake, and AEG-1 sequence-specific knockdown in 143B cells, with transfection efficiencies comparable to those of commercial lipofectamine but with lower cytotoxicity. This AEG-1-focused RNAi therapy supplemented with chemotherapy inhibited, and was effective in inhibiting the growth in of osteosarcoma xenografts mouse models. The combination therapy is an alternative or combinatorial strategy that can produce durable inhibitory responses in osteosarcoma patients.

Synthesis, physiochemical characterization, molecular docking study, and anti-breast cancer activity of silymarin loaded zein nanoparticles.

Breast cancer is a major cause of death in women worldwide leading to requirement of new therapeutic strategies. Silymarin demonstrated the anti-cancer activity however, due to low bioavailability its use is restricted. This study aimed to improve the solubility of silymarin by developing a silymarin loaded zein nanoparticles (SLNPs) which was stabilized by beta cyclodextrin. Comprehensive physiochemical characterization studies based on DLS, FTIR, UV-Vis Spectroscopy, FE-SEM, TEM, XRD, DSC, NMR and TGA confirmed the successful synthesis of SLNPs via an anti-solvent precipitation method. FE-SEM and TEM images demonstrated the uniform size and spherical shape of nanoparticles with encapsulation and loading efficiencies of 84.32 ± 1.9 % and 15.25 ± 2.4 % respectively. The zein protein interaction with silymarin, and ß-cyclodextrin was shown to be beneficial via the use of molecular simulations and binding energy calculations. Cellular studies demonstrated dose and time dependent cytotoxicity of SLNPs on MCF-7 breast cancer cell. FACS, qRT-PCR and Western blotting showed Bax (pro-apoptotic) upregulation while Bcl-2 (anti-apoptotic) downregulation. Our findings suggest that these loaded nanoparticles are more efficient than pure drug, enhancing its bioavailability and paving the path for developing it as a promising nutraceutical to treat breast cancer.