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The present study aims to develop a novel nanocombination with high selectivity against several invasive cancer cells, sparing normal cells and tissues. Bovine lactoferrin (bLF) has recently captured the interest of numerous medical fields owing to its biological activities and well-known immunomodulatory effects. BLF is an ideal protein to be encapsulated or adsorbed into selenium nanocomposites (Se NPs) in order to produce stable nanocombinations with potent anticancer effects and improved immunological functions. The biosynthesis of the functionalized Se NPs was achieved using Rhodotorula sp. strain MZ312359 via a simultaneous bio-reduction approach to selenium sodium salts. The physicochemical properties of Se NPs using SEM, TEM, FTIR, UV Vis, XRD, and EDX confirmed the formation of uniform agglomerated spheres with a size of 18-40 nm. Se NPs were successfully embedded in apo-LF (ALF), forming a novel nanocombination of ALF-Se NPs with a spherical shape and an average nanosize of less than 200 nm. The developed ALF-Se NPs significantly displayed an effective anti-proliferation efficiency against many cancer cells, including MCF-7, HepG-2, and Caco-2 cell lines, as compared to Se NPs and ALF in free forms. ALF-Se NPs showed a significant selectivity impact (> 64) against all treated cancer cells at IC 50 63.10 ≤ μg/mL, as well as the strongest upregulation of p53 and suppression of Bcl-2, MMP-9, and VEGF genes. Besides, ALF-Se NPs were able to show the maximum activation of transcrition of key redox mediator (Nrf2) with suppression in reactive oxygen species (ROS) levels inside all treated cancer cells. This study demonstrates that this novel nanocombination of ALF-Se NPs has superior selectivity and apoptosis-mediating anticancer activity over free ALF or individual form of Se NPs., (© 2023. The Author(s).)

The promising features of most bacterial celluloses (BC) promote the continuous mining for a cost-effective production approach toward wide and sustainable applications. Herein, cantaloupe peels (CP) were successfully implemented for sustainable BC production. Results indicated that the enzymatically hydrolyzed CP supported the maximum BC production of approximately 3.49 g/L when used as a sole fermentation media. The produced BC was fabricated with polyvinyl alcohol (PVA) and chitosan (Ch), and loaded with green synthesized copper oxide nanoparticles (CuO-NPs) to improve its biological activity. The novel composite showed an antimicrobial activity against several human pathogens such as Staphylococcus aureus, Streptococcus mutans, Salmonella typhimurium, Escherichia coli, and Pseudomonas fluorescens. Furthermore, the new composite revealed a significant in vitro anticancer activity against colon (Caco-2), hepatocellular (HepG-2), and breast (MDA) cancer cells, with low IC 50 of 0.48, 0.27, and 0.33 mg/mL for the three cell lines, respectively. On the other hand, the new composite was remarkably safe for human skin fibroblast (HSF) with IC 50 of 1.08 mg/mL. Interestingly, the composite membranes exhibited lethal effects against all stages of larval instar and pupal stage compared with the control. In this study, we first report the diverse potential applications of BC/PVA/Ch/CuO-NPs composites based on green synthesized CuO-NPs and sustainably produced BC membrane., (© 2022. The Author(s).)

The prevalence of opportunistic human fungal pathogens is increasing worldwide, and antimicrobial resistance is one of the greatest medical challenges the world faces. Therefore, this study aimed to develop a novel agent to control fungal pathogens. The honeybee products (honey, royal jelly, propolis, bee bread, and bee venom) were screened against unicellular fungal (UCF) pathogens (Cryptococcus neoformans, Kodamaea ohmeri, and Candida albicans) and the bee venom was only exhibited an inhibitory effect against them. The protein contents of crude bee venom were separated using the gel filtration technique into eight fractions which were visualized on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) to confirm the presence of five bands with molecular weights of 65, 43, 21, 15, and 3 KDa. Bee venom (BV) of Apis mellifera loaded chitosan nanoparticles were prepared by the ionotropic gelation method. The encapsulation efficiency%, average size, zeta potentials, and surface appearance by Transmission electron microscope (TEM) were evaluated for the prepared nanoparticles. The minimum inhibitory concentration (MIC) of crude BV and BV loaded chitosan nanoparticles (BV-CNPs) was evaluated against the offer mentioned UCF where the MIC values of crude BV were 6.25, 3.12 & 6.25 while MIC values in the case of BV-CNPs were decreased to 3.12, 3.12 & 1.56 mg/ml against C. neoformans, K. ohmeri and C. albicans, respectively. Also, the results showed that BV-CNPs suppressed the biofilm formation as well as yeast to hyphal transition formed by the examined UCF. These results revealed that BV-CNPs are a promising natural compound for fungal pathogens treatment., (© 2022. The Author(s).)

Lactoperoxidase is a glycosylated protein with a molecular mass of 78 kDa, which being excreted in several mammalian secretions. Lactoperoxidase is included in many biological processes and well-known to have biocidal actions, attending as active antibiotics and antiviral agents. This wide-spectrum of biocidal activities mediates via a definite inhibitory system named lactoperoxidase system which acts a potent role in the innate immune response since its activity is not restricted by the antimicrobial effect, but might act a significant role in the hydrolysis of many toxins like aflatoxin. Hence with the current progresses in technology, nanoparticles can offer chances as an active candidate that might be utilized for stabilizing and potentiating the activity of LPO for use in several applications. Due to the variability functions of LPO, this enzyme considers an active target to be encapsulated or coated to NPs for developing novel nanocombinations with controlled surface characteristics. The development of approaches which might enhance conformational stabilization for several weeks of LPO via nanoformulation could improve the biopharmaceutical applicability of this bioactive ingredient. Nanoformulation of LPO enhances novel functions that can be useful in many biotechnological applications like food industry, cosmetic and pharmaceutical applications or to deliver and encapsulate bioactive components.

Lactoferrin is a glycoprotein with a molecular weight of 80 kDa, which produced in many mammalian excretions. LF is involved in various physiological processes and known to possess prominent biocidal activities, serving as an effective agent against a wide range of pathogens. This effective biocidal activity of LF in association with immune system response has made this protein an attractive therapeutic candidate. Interaction of proteins with nanoparticles (NPs) gives rise to the formation of a dynamic NP-protein complex and can induce conformational changes in the adsorbed proteins which may lead to the change in their function. With the recent advances in nanotechnology, NPs may provide the protection and stabilization of LF from hydrolysis by some proteases and increase their uptake by targeted cells. These nanoformulations of LF can be used as diagnosis, disease targeting and drug delivery tools. Owing to its multiple functionalities, LF is a promising active ingredient to be loaded or adsorbed to NPs for preparing a stable, controlled surface NPs. Thus, LF NPs can potentially empower the resulting nanocomplex with attracting functionalities and might be useful in many applications, e.g., to modify the optical or rheological properties of products, or to encapsulate and deliver bioactive ingredients., Competing Interests: Declaration of competing interest The author declares that there is no conflict of interest regarding the publication of this review manuscript., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Hyaluronic acid (HA) based nanofibers (NFs) represented a novel class of bioactive wound dressings that have a vital role in wound management due to their unique properties as an extracellular-matrix and accelerating wound healing. Novel L-arginine-loaded citric acid crosslinked PVA-HA NFs were fabricated by electrospinning and proposed for potential wound healing purposes. However, poor mechanical properties of HA NFs might limit its biological usage, thus this study aims to develop reinforced PVA/HA NFs by incorporation of cellulose nanocrystals (CNCs) as nanofiller and loading L-arginine as wound healing accelerator. Results revealed that incorporation of CNCs into PVA/HA significantly improved mechanical and swelling properties of NFs, compared to CNC-free NFs. Biological performance of NFs was evaluated on normal human skin melanocyte (HFB-4) and lung fibroblast (WI38) cell-lines. PVA/HA/CNC/L-arginine NFs exhibited excellent hemocompatibility, high protein adsorption, outstanding proliferative and adhesive potential on HFB-4 cells expressed by high wound gap-closure 99.9% after 48 h of exposure. Released arginine from PVA/HA/CNC NFs showed sustained release about 46.5% and ~90% after 24 h and 48 h, respectively. Briefly, PVA/HA/CNCs/L-arginine showed adequate antibacterial activity especially against Klebsiella pneumonia, as an acute popular pathogen causing a skin infection. These results indicate that PVA/HA/CNC/L-arginine could act as promising and multifunctional wound dressings., Competing Interests: Declaration of competing interest The authors declare no competing or financial interests., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Interaction between nanoparticles (NPs) and protein is particularly important due to the formation of dynamic nanoparticle-protein complex. The current study indicated that silica NPs were able to induce conformational modification in the adsorbed lactoperoxidase (LPO) which in turns degrades the synthetic dyes. The maximum degradation efficiency was recorded for the LPO modified silica NPs in the presence of H 2 O 2 comparing with either free LPO or silica NPs. Degradation efficiency of crystal violet and commassie blue R250 after 6 h was assessed to be 100(%). Also, degradation efficiency of Congo red reached 90.6% and 79.3% in the presence and absence of H 2 O 2 , respectively, however methyl red degradation efficiency recorded 85%. The viability assay experiment indicated that the IC 50 value of the LPO modified silica NPs on human fibroblast cells reached 2.8 mg/ml after 48 h incubation. In addition to dye removal, the LPO modified silica NPs were able to inhibit the antibiotic resistant bacterial strains (Salmonell typhii, Staphylococcus areus, Pseudomonas aureginosa, E. coli, Proteus sp. and streptococcus sp.) at concentrations up to 2.5 mg/ml with inhibition activity about 95%. These findings emphasized that the ability of LPO for degradation of the synthetic dyes after adsorption on silica NPs besides it could be a promising agent with potent inhibitory effect targeting a wide range of multidrug resistant bacteria.

Bovine lactoperoxidase (LPO) and lactoferrin (LF) are suitable proteins to be loaded or adsorbed to chitosan nanoparticles (NPs) for preparing stable nanoformulations with potent anticancer activity. In the present study, nanocombinations of LPO and LF revealed improvement in their stability and activity compared to single (free or nanoformulated) bovine proteins. The coating or loading of LPO-loaded NPs with LF resulted in the highest synergistic cytotoxicity effect against Caco-2, HepG-2, MCF-7 and PC-3 cells in comparison with other NPs and free proteins without causing toxicity toward normal cells. This synergistic improvement in the anticancer activity was apoptosis-dependent that was confirmed by severe alterations in cellular morphology, high percentage of annexin-stained cells and sub-G1 populations as well as nuclear staining with orange fluorescence of treated cancer cells. Additionally, significant alterations in the expression of well characterized cellular proliferation and apoptosis guards (NF-κB, Bcl-2 and p53) in these NPs-treated cancer cells compared to 5-fluorouracil (5-FU) treated cells. Our findings provide for the first time that these new synergistic nanoformulated forms of LPO and LF were superior in their selective apoptosis-mediating anticancer effect than free form of these proteins and 5-FU. LF coating or loading of LPO-loaded NPs present as promising therapy for cancer.