The use of proteins and peptides-based therapy in managing and preventing pathogenic viruses.

Therapeutic proteins have been employed for centuries and reached approximately 50 % of all drugs investigated. By 2023, they represented one of the top 10 largest-selling pharma products ($387.03 billion) and are anticipated to reach around $653.35 billion by 2030. Growth hormones, insulin, and interferon (IFN α, γ, and ß) are among the leading applied therapeutic proteins with a higher market share. Protein-based therapies have opened new opportunities to control various diseases, including metabolic disorders, tumors, and viral outbreaks. Advanced recombinant DNA biotechnology has offered the production of therapeutic proteins and peptides for vaccination, drugs, and diagnostic tools. Prokaryotic and eukaryotic expression host systems, including bacterial, fungal, animal, mammalian, and plant cells usually applied for recombinant therapeutic proteins large-scale production. However, several limitations face therapeutic protein production and applications at the commercial level, including immunogenicity, integrity concerns, protein stability, and protein degradation under different circumstances. In this regard, protein-engineering strategies such as PEGylation, glycol-engineering, Fc-fusion, albumin conjugation, and fusion, assist in increasing targeting, product purity, production yield, functionality, and the half-life of therapeutic protein circulation. Therefore, a comprehensive insight into therapeutic protein research and findings pave the way for their successful implementation, which will be discussed in the current review.

Therapeutic efficacy of α-lactalbumin coated oleic acid based liposomes against colorectal carcinoma in Caco-2 cells and DMH-treated albino rats.

Colorectal cancer (CRC) is a malignant tumor recognized as a major cause of morbidity and mortality throughout the world. Therefore, novel liposomes of oleic acid coated with camel α-lactalbumin (α-LA coated liposomes) were developed for their potential antitumor activity against CRC, both in vitro and in DMH-induced CRC-modeled animal. In vitro results indicated the high safety of α-LA coated liposomes towards normal human cells with potent antitumor activity against Caco-2 cells at an IC50 value of 57.01 ± 3.55 µM with selectivity index of 6.92 ± 0.48. This antitumor activity has been attributed to induction of the apoptotic mechanism, as demonstrated by nuclear condensation and arrest of Caco-2 cells in sub-G1 populations. α-LA coated liposomes also revealed a significant up-regulation of the p53 gene combined with a down-regulation of the Bcl2 gene. Moreover, in vivo results revealed that treatment of induced-CRC modeled animals with α-LA coated liposomes for six weeks markedly improved the CRC-disorders; this was achieved from the significant reduction in the values of AFP, CEA, CA19.9, TNF-α, IL-1ß, MDA, and NO coupled with remarkable rise in SOD, GPx, GSH, CAT, and CD4+ levels. The histopathological findings asserted the therapeutic potential of α-LA coated liposomes in the treatment of CRC. Therefore, the present results proved the antitumor activity of α-LA coated liposomes against CRC through the restoration of impaired oxidative stress, improved immune response, and reduced inflammation.Communicated by Ramaswamy H. Sarma.

Protective Activity of Rhizobium leguminosarum bv. viciae Strain 33504-Mat209 against Alfalfa Mosaic Virus Infection in Faba Bean Plants.

The application of Rhizobium spp., nitrogen-fixing plant growth-promoting rhizobacteria, as biocontrol agents to enhance systemic disease resistance against plant viral infections is a promising approach towards achieving sustainable and eco-friendly agriculture. However, their potential as antivirals and biocontrol agents is less studied. Herein, the capability of Rhizobium leguminosarum bv. viciae strain 33504-Mat209 was evaluated to promote plant growth and enhance faba bean systemic resistance against alfalfa mosaic virus (AMV) infection. Under greenhouse conditions, the soil inoculation with 3504-Mat209 resulted in notable improvements in growth and an increase in chlorophyll content. This led to a marked decrease in the disease incidence, severity, and viral accumulation level by 48, 74, and 87%, respectively. The protective effect of 33504-Mat209 was linked to significant decreases in non-enzymatic oxidative stress indicators, specifically H2O2 and MDA. Additionally, there were significant increases in the activity of reactive oxygen species scavenging enzymes, such as peroxidase (POX) and polyphenol oxidase (PPO), compared to the virus treatment. The elevated transcript levels of polyphenolic pathway genes (C4H, HCT, C3H, and CHS) and pathogenesis-related protein-1 were also observed. Out of 18 detected compounds, HPLC analysis revealed that 33504-Mat209-treated plants increased the accumulation of several compounds, such as gallic acid, chlorogenic acid, catechin, pyrocatechol, daidzein, quercetin, and cinnamic acid. Therefore, the ability of 33504-Mat209 to promote plant growth and induce systemic resistance against AMV infection has implications for utilizing 33504-Mat209 as a fertilizer and biocontrol agent. This could potentially introduce a new strategy for safeguarding crops, promoting sustainability, and ensuring environmental safety in the agricultural sector. As far as we know, this is the first study of biological control of AMV mediated by Rhizobium spp. in faba bean plants.

In Vitro and In Vivo Synergistic Antitumor Activity of Albumin-Coated Oleic Acid-Loaded Liposomes toward Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most lethal and prevalent cancers, closely associated with cirrhosis and fibrosis. This study aimed to assess the antitumor activity of oleic acid-liposomes (uncoated liposomes) upon coating with albumin against HCC. The in vitro studies revealed the high safety of the prepared uncoated and albumin-coated liposomes to normal HFB-4 cells (EC100 of 35.57 ± 0.17 and 79.133 ± 2.92 µM, respectively) with significant anticancer activity against HepG-2 cells with IC50 of 56.29 ± 0.91 and 26.74 ± 0.64 µM, respectively. The albumin-coated liposomes revealed superior apoptosis induction potential (80.7%) with significant upregulation of p53 gene expression (>7.0-fold), compared to OA. The in vivo study revealed that the administration of uncoated or albumin-coated liposomes (100 mg/kg) for six weeks markedly retarded the DENA-induced HCC in Wistar albino rates through regulating the liver enzymes, total bilirubin level, pro-inflammatory cytokines, and oxidative stress. Accordingly, the current study supports the in vitro and in vivo chemo-preventive feature of albumin-coated liposomes against HCC through modulation of apoptosis, improvement of the immune response, reduction of inflammation, and restoration of impaired oxidative stress, which is the first reported to the best of our knowledge.

Antiviral Activity of Biosynthesized Silver Nanoparticles from Pomegranate (Punica granatum L.) Peel Extract against Tobacco Mosaic Virus.

Tobacco mosaic virus (TMV) is a major pathogen affecting tomato plants worldwide. The efficacy of silver nanoparticles (Ag-NPs) mediated by Punica granatum biowaste peel extract in mitigating the negative impact of TMV infection on tomato growth and oxidative stress was investigated through scanning electron microscopy (SEM), transmission electron microscopy (TEM), UV-Visible (UV-Vis) spectrophotometer, X-ray Diffraction (XRD), dynamic light scattering (DLS), zeta potential, energy-dispersive X-ray spectroscopy (EDX), and Fourier-transform infrared spectra (FTIR). Results of SEM analysis of green Ag-NPs revealed the presence of condensed spherical or round NPs with diameters ranging between 61 and 97 nm. TEM confirmed the SEM results and showed round-shaped Ag-NPs with an average size of 33.37 ± 12.7 nm. The elemental analysis (EDX) of prepared Ag-NPs revealed the presence of elemental Ag as a major peak (64.43%) at 3-3.5 KeV. The FTIR revealed several functional groups on the prepared Ag-NPs, for which three treatment strategies for Ag-NP applications were evaluated in the greenhouse study and compared to inoculated TMV and control plants: pre-infection treatment (TB), post-infection treatment (TA), and dual treatment (TD). The results showed that the TD strategy is the most effective in improving tomato growth and reducing viral replication, whereas all Ag-NP treatments (TB, TA, and TD) were found to significantly increase expression of the pathogenesis-related (PR) genes PR-1 and PR-2, as well as polyphenolic compounds, HQT, and C4H genes compared to control plants. In contrast, the flavonoid content of tomato plants was not affected by the viral infection, while the phenolic content was significantly reduced in the TMV group. Furthermore, TMV infection led to a significant increase in oxidative stress markers MDA and H2O2, as well as a reduction in the enzymatic activity of the antioxidants PPO, SOD, and POX. Our results clearly showed that the application of Ag-NPs on TMV-infected plants reduces virus accumulation, delays viral replication in all treatments, and greatly enhances the expression of the CHS gene involved in flavonoid biosynthesis. Overall, these findings suggest that treatment with Ag-NPs may be an effective strategy to mitigate the negative impact of TMV infection on tomato plants.

Palm Fruit (Phoenix dactylifera L.) Pollen Extract Inhibits Cancer Cell and Enzyme Activities and DNA and Protein Damage.

Palm fruit pollen extract (PFPE) is a natural source of bioactive polyphenols. The primary aim of the study was to determine the antioxidant, antimicrobial, anticancer, enzyme inhibition, bovine serum albumin (BSA), and DNA-protective properties of PFPE and identify and quantify the phenolic compounds present in PFPE. The results demonstrated that PFPE exhibited potent antioxidant activity in various radical-scavenging assays, including (2,2-diphenyl-1-picrylhydrazyl) (DPPH•), 2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS•), nitric oxide (NO), ferric-reducing/antioxidant power (FRAP), and total antioxidant capacity (TAC). PFPE also displayed antimicrobial activity against several pathogenic bacteria. Similarly, PFPE reduced acetylcholinesterase, tyrosinase, and α-amylase activities. PFPE has been proven to have an anticancer effect against colon carcinoma (Caco-2), hepatoma (HepG-2), and breast carcinoma (MDA) cancer cells. Apoptosis occurred in PFPE-treated cells in a dose-dependent manner, and cell cycle arrest was observed. Furthermore, in breast cancer cells, PFPE down-regulated Bcl-2 and p21 and up-regulated p53 and Caspase-9. These results show that PFPE constitutes a potential source of polyphenols for pharmaceutical, nutraceutical, and functional food applications.

Antioxidant, Anti-Inflammatory, Antimicrobial, and Anticancer Activities of Pomegranate Juice Concentrate.

Pomegranate juice concentrate (PJC) is a rich source of polyphenols, which exhibit significant antioxidant activity and potential health benefits for disease prevention and therapy. In this study, the polyphenolic profile of PJC was investigated for the first time, and it was found that PJC can inhibit oxidative damage to bovine serum albumin (BSA) and deoxyribonucleic acid (DNA), as well as acetylcholinesterase, α-amylase, and tyrosinase activities. The primary polyphenols identified in PJC were 4-Hydroxy-3-Methoxybenzoate, epicatechin, catechin, rutin, ferulic acid, P-coumaric acid, and cinnamic acid. Additionally, PJC demonstrated potent antibacterial effects against human pathogens such as Streptococcus mutans and Aeromonas hydrophila and dose-dependently reduced the proliferation of colorectal, breast, and hepatic cancer cells via apoptosis. Furthermore, PJC blocked B-cell lymphoma 2 (BCl-2) and the expression of a potent cyclin-dependent kinase inhibitor (P21) and enhanced tumor protein (P53) expression, compared to both untreated cells and cells treated with fluoropyrimidine 5-fluorouracil (5-FU). As a result, PJC may be a beneficial ingredient in the formulation of emerging natural-compound-based chemotherapy and functional foods and could be utilized by the food, nutraceutical, and pharmaceutical industries.

Statistical optimization and characterization of fucose-rich polysaccharides extracted from pumpkin (Cucurbita maxima) along with antioxidant and antiviral activities.

Biologically active phytochemicals from pumpkin reveal versatile medical applications, though little is known about their antiviral activity. The fucose-rich polysaccharide extraction conditions were optimized through Box-Behnken design and purified by column chromatography. The purified fucose-rich polysaccharide was characterized through SEM, FT-IR, 1H NMR, XRD, TGA, and GS-MS. The analysis results revealed an irregular and porous surface of the purified polysaccharide with high fucose, rhamnose, galactose, and glucose contents. The tested fucose-rich polysaccharides revealed significant antioxidant and anti-inflammatory activity at very low concentrations. The purified fucose-rich polysaccharides exerted a broad-spectrum antiviral activity against both DNA and RNA viruses, accompanied by high safety toward normal cells, where the maximum safe doses (EC100) were estimated to be about 3-3.9 mg/mL for both Vero and PBMC cell lines. Treatment of HCV, ADV7, HSV1, and HIV viruses with the purified polysaccharides showed a potent dose-dependent inhibitory activity with IC50 values of 95.475, 20.96, 5.213, and 461.75 µg/mL, respectively. This activity was hypothesized to be through inhibiting the viral entry in HCV infection and inhibiting the reverse transcriptase activity in HIV. The current study firstly reported the antioxidant, anti-inflammatory, and antiviral activities of Cucurbita maxima fucose-rich polysaccharide against several viral infections.

Exploitation of cantaloupe peels for bacterial cellulose production and functionalization with green synthesized Copper oxide nanoparticles for diverse biological applications.

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 IC50 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 IC50 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.

Ocimum basilicum-Mediated Synthesis of Silver Nanoparticles Induces Innate Immune Responses against Cucumber Mosaic Virus in Squash.

Cucumber mosaic virus (CMV) causes a significant threat to crop output sustainability and human nutrition worldwide, since it is one of the most prevalent plant viruses infecting most kinds of plants. Nowadays, different types of nanomaterials are applied as a control agent against different phytopathogens. However, their effects against viral infections are still limited. In the current study, the antiviral activities of the biosynthesized silver nanoparticles (Ag-NPs) mediated by aqueous extract of Ocimum basilicum against cucumber mosaic virus in squash (Cucurbita pepo L.) were investigated. The prepared Ag-NPs were characterized using scanning electron microscopy (SEM), dynamic light scattering (DLS), transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDX), Fourier transform infrared spectroscopy (FTIR) and zeta potential distribution techniques. DLS, SEM, and TEM analyses showed that the Ag-NPs were spherical, with sizes ranging from 26.3 to 83 nm with an average particle size of about 32.6 nm. FTIR identified different functional groups responsible for the capping and stability of Ag-NPs. The zeta potential was reported as being -11.1 mV. Under greenhouse conditions, foliar sprays of Ag-NPs (100 µg/mL) promoted growth, delayed disease symptom development, and significantly reduced CMV accumulation levels of treated plants compared to non-treated plants. Treatment with Ag-NPs 24 h before or after CMV infection reduced CMV accumulation levels by 92% and 86%, respectively. There was also a significant increase in total soluble carbohydrates, free radical scavenging activity, antioxidant enzymes (PPO, SOD, and POX), as well as total phenolic and flavonoid content. Furthermore, systemic resistance was induced by significantly increasing the expression levels of pathogenesis-related genes (PR-1 and PR-5) and polyphenolic pathway genes (HCT and CHI). These findings suggest that Ag-NPs produced by O. basilicum could be used as an elicitor agent and as a control agent in the induction and management of plant viral infections.

Protective and Curative Activities of Paenibacillus polymyxa against Zucchini yellow mosaic virus Infestation in Squash Plants.

The use of microbial products as natural biocontrol agents to increase a plant's systemic resistance to viral infections is a promising way to make agriculture more sustainable and less harmful to the environment. The rhizobacterium Paenibacillus polymyxa has been shown to have strong biocontrol action against plant diseases, but its antiviral activity has been little investigated. Here, the efficiency of the culture filtrate of the P. polymyxa strain SZYM (Acc# ON149452) to protect squash (Cucurbita pepo L.) plants against a Zucchini yellow mosaic virus (ZYMV, Acc# ON159933) infection was evaluated. Under greenhouse conditions, the foliar application of the culture filtrate of SZYM either in protective or curative treatment conditions enhanced squash growth, reduced disease severity, and decreased ZYMV accumulation levels in the treated plants when compared to the non-treated plants. The protective treatment group exhibited the highest inhibitory effect (80%), with significant increases in their total soluble carbohydrates, total soluble protein content, ascorbic acid content, and free radical scavenging activity. Furthermore, a considerable increase in the activities of reactive oxygen species scavenging enzymes (superoxide dismutase, polyphenol oxidase, and peroxidase) were also found. In addition, the induction of systemic resistance with a significant elevation in the transcriptional levels of polyphenolic pathway genes (CHS, PAL, and C3H) and pathogenesis-related genes (PR-1 and PR-3) was observed. Out of the 14 detected compounds in the GC-MS analysis, propanoic acid, benzenedicarboxylic acid, tetradecanoic acid, and their derivatives, as well as pyrrolo [1,2-a] pyrazine-1,4-dione, hexahydro-3-(2-methylpropyl) were the primary ingredient compounds in the ethyl acetate extract of the SZYM-culture filtrate. Such compounds may act as elicitor molecules that induce systemic resistance against viral infection. Consequently, P. polymyxa can be considered a powerful plant growth-promoting bacterium (PGPB) in agricultural applications as well as a source of bioactive compounds for sustainable disease management. As far as we know, this is the first time that P. polymyxa has been shown to fight viruses in plants.

Enhancing systemic resistance in faba bean (Vicia faba L.) to Bean yellow mosaic virus via soil application and foliar spray of nitrogen-fixing Rhizobium leguminosarum bv. viciae strain 33504-Alex1.

Rhizobium spp. manifests strong nitrogen fixation ability in legumes. However, their significance as biocontrol agents and antivirals has rarely been investigated. Under greenhouse conditions, the molecularly identified nitrogen-fixing plant growth-promoting rhizobacteria (PGPR), Rhizobium leguminosarum bv. viciae strain 33504-Alex1, isolated from the root nodules of faba bean plants, was tested as a soil inoculum or a foliar application to trigger faba bean plants' resistance against Bean yellow mosaic virus (BYMV) infection. Compared to the non-treated faba bean plants, the applications of 33504-Alex1 in either soil or foliar application significantly promoted growth and improved total chlorophyll content, resulting in a considerable reduction in disease incidence and severity and the inhibition index of BYMV in the treated faba bean plants. Furthermore, the protective activities of 33504-Alex1 were associated with significant reductions in non-enzymatic oxidative stress markers [hydrogen peroxide (H2O2) and malondialdehyde (MDA)] and remarkably increased DPPH free radical scavenging activity and total phenolic content compared to the BYMV treatment at 20 days post-inoculation. Additionally, an increase in reactive oxygen species scavenging enzymes [superoxide dismutase (SOD) and polyphenol oxidase (PPO)] and induced transcriptional levels of pathogenesis-related (PR) proteins (PR-1, PR-3, and PR-5) were observed. Of the 19 polyphenolic compounds detected in faba bean leaves by high-performance liquid chromatography (HPLC) analysis, gallic and vanillic acids were completely shut down in BYMV treatment. Interestingly, the 33504-Alex1 treatments were associated with the induction and accumulation of the most detected polyphenolic compounds. Gas chromatography-mass spectrometry (GC-MS) analysis showed hexadecanoic acid 2,3-dihydroxypropyl ester, tetraneurin-A-Diol, oleic acid, and isochiapin B are the major compounds in the ethyl acetate extract of 33504-Alex1 culture filtrate (CF), suggesting it acts as an elicitor for the induction of systemic acquired resistance (SAR) in faba bean plants. Consequently, the capacity of R. leguminosarum bv. viciae strain 33504-Alex1 to enhance plant growth and induce systemic resistance to BYMV infection will support the incorporation of 33504-Alex1 as a fertilizer and biocontrol agent and offer a new strategy for crop protection, sustainability, and environmental safety in agriculture production.

Synthesis, and docking studies of novel heterocycles incorporating the indazolylthiazole moiety as antimicrobial and anticancer agents.

The current study was directed toward developing a new series of fused heterocycles incorporating indazolylthiazole moiety. The newly synthesized compounds were characterized through elemental analysis and spectral data (IR, 1H-NMR, 13C-NMR, and Mass Spectrometry). The cytotoxic effect of the newly synthesized compounds was evaluated against normal human cells (HFB-4) and cancer cell lines (HepG-2 and Caco-2). Among the synthesized compounds, derivatives 4, and 6 revealed a significant selective antitumor activity, in a dose-dependent manner, against both HepG-2 and Caco-2 cell lines, with lower risk toward HFB-4 cells (normal cells). Derivative 8 revealed the maximum antitumor activity toward both tumor cell lines, with an SI value of about 26 and IC50 value of about 5.9 µg/mL. The effect of these derivatives (8, 4, and 6) upon the expression of 5 tumor regulating genes was studied through quantitative real-time PCR, where its interaction with these genes was simulated through the molecular docking study. Furthermore, the antimicrobial activity results revealed that compounds 2, 7, 8, and 9 have a potential antimicrobial activity, with maximum broad-spectrum activity through compound 3 against the three tested pathogens: Streptococcus mutans, Pseudomonas aeruginosa, and Candida albicans. The newly prepared compounds also revealed anti-biofilm formation activity with maximum activity against Streptococcus mutans, Pseudomonas aeruginosa, and Candida albicans, respectively.

Fabrication, characterization and in vitro evaluation of disulfiram-loaded cellulose acetate/poly(ethylene oxide) nanofiber scaffold for breast and colon cancer cell lines treatment.

Cancer and microbial infections threaten human health. Currently, chemotherapeutic drugs for cancer lack selectivity between normal and cancer cells, exacerbating this problem. Effective anticancer drug encapsulation is the golden key to solving this issue. Disulfiram (DS), an anticancer drug, has low solubility and selectivity and to tackle this concern, cellulose acetate (CA) and poly (ethylene oxide) (PEO) was selected as a matrix to prepare nanofiber containing DS (DS@CA/PEO) via electrospinning technique. DS@CA/PEO nanofiber was characterized by SEM, FTIR, TGA, and X-rd patterns and the results confirmed DS incorporation in CA/PEO nanofiber. DS@CA/PEO nanofiber scaffold showed higher safety than DS-free on human normal cells (Wi-38) with revealing similar anticancer activity of DS-free against colon cancer line (Caco-2) and breast cancer line (MDA-MB 231). This higher selectivity of DS@CA/PEO towards cancer cells than normal cells was associated with maintaining apoptotic activity and aldehyde dehydrogenase-inhibitory potency of DS. The latter efficacy led to eradicating colon and breast cancer stem cells, as evidenced by flow cytometry. Moreover, DS@CA/PEO nanofiber scaffold showed potent antibacterial activity (in vitro) against both Gram-negative and Gram-positive bacteria. These results investigated that DS@CA/PEO nanofiber scaffold could be a potential dual candidate as a selective anticancer and antimicrobial agent.

Novel Nanocombinations of l-Tryptophan and l-Cysteine: Preparation, Characterization, and Their Applications for Antimicrobial and Anticancer Activities.

Tungsten oxide WO3 nanoparticles (NPs) were prepared in a form of nanosheets with homogeneous size and dimensions in one step through acid precipitation using a cation exchange column. The resulting WO3 nanosheet surface was decorated with one of the two amino acids (AAs) l-tryptophan (Trp) or l-cysteine (Cys) and evaluated for their dye removal, antimicrobial, and antitumor activities. A noticeable improvement in the biological activity of WO3 NPs was detected upon amino acid modification compared to the original WO3. The prepared WO3-Trp and WO3-Cys exhibited strong dye removal activity toward methylene blue and safranin dyes with complete dye removal (100%) after 6 h. WO3-Cys and WO3-Trp NPs revealed higher broad-spectrum antibacterial activity toward both Gram-negative and Gram-positive bacteria, with strong antifungal activity toward Candida albicans. Anticancer results of the modified WO3-Cys and WO3-Trp NPs against various kinds of cancer cells, including MCF-7, Caco-2, and HepG-2 cells, indicate that they have a potent effect in a dose-dependent manner with high selectivity to cancer cells and safety against normal cells. The expression levels of E2F2 and Bcl-2 genes were found to be suppressed after treatment with both WO3-Cys and WO3-Trp NPs more than 5-FU-treated cells. While expression level of the p53 gene in all tested cells was up-regulated after treatment 5-8 folds more as compared to untreated cells. The docking results confirmed the ability of both NPs to bind to the p53 gene with relevant potency in binding to other tested gens and participation of cysteine SH-functional group in such interaction.