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Cardiovascular diseases (CVDs) have been ranked as the leading cause of death in the world, whose global incidence is increasing year by year. Citrus, one of the most popular fruits in the world, is rich in flavonoids. Citrus flavonoids attract special attention due to a variety of biological activities, especially in the prevention and treatment of CVDs. The research progress of citrus flavonoids on CVDs have been constantly updated, but relatively fragmented, which needed to be systematically summarized. Hence, the recent research about citrus flavonoids and CVDs were reviewed, including the types and in vivo processes of citrus flavonoids, epidemiology study and mechanism on prevention and treatment of CVDs by citrus flavonoids. This review would provide a theoretical basis for the citrus flavonoids research and a new idea in the citrus industry development and application.

The aim of this study is to investigate whether Flammuliana Velutipes Polysaccharide (FVP) could aid in the prevention of colitis. Effect of FVP on colitis was evaluated using dextran sulfate sodium (DSS)-induced colitis in rats. Influence of FVP on the expression of inflammation related biomarkers and signal pathway element of TLR4\NF-κB were assessed. The composition and taxonomy of colonic microbiota were analyzed by 16S rDNA high throughput sequencing, and the concentrations of caecal short fatty chain acids were assessed by chromatography-mass spectrometry. Our results showed that FVP treatment could regulate the colonic microbial dysbiosis and promote the levels of caecal short fatty chain acids, leading to down-regulation of TLR4\NF-κB signal pathway, which finally ameliorate the colitis. Thus, the present study is the first attempt to elucidate the effect of FVP on colitis and support the potential application of FVP as a functional food ingredient or preventive drugs for colitis.

Multidrug resistance (MDR), defined as the cross-resistance of cancer cells toward a broad range of chemotherapeutic agents, is a universal and intractable problem in chemotherapy. The understanding of MDR mechanisms is essential to discover the potential biomarkers for predicting multidrug resistance and more importantly, tackling and preventing multidrug resistance. Multiple technologies have been used to study MDR mechanisms including comparative genomic hybridization, DNA array, differential display RT-PCR and various immunoassays. Compared with these approaches, proteomic technologies allow a high through-put analysis of protein detection, protein quantification and protein interaction with high accuracy. With the rapid development of proteomic studies in recent years, proteomic technologies have made substantial contributions to the characterization of MDR mechanisms including MDR-related protein detection and quantification, as well as the characterization of drug-transporter binding sites. This review offers a comprehensive illustration of MDR, proteomic technologies and the discoveries made in understanding MDR mechanisms using proteomic approaches.

The effects of a novel Flammulina velutipes polysaccharide (FVP) on intestinal microbiota, immune repertoire and heart transcriptome were investigated in this study. The results showed that FVP treatment could effectively regulate the abundance of colonic microbiota. And FVP exhibited obvious immunoregulatory effect by influencing V gene and J gene fragments usage on TCRα chain. The usage frequency of TRBV1, TRBJ1-6 and TRBJ1-5 were significantly altered, and 41 V-J pairs were identified with obvious difference after FVP treatment. Furthermore, the mRNA of mice heart was analyzed by transcriptome assay. Total 525 genes and 1587 mRNA were significantly changed after FVP treatment. KEGG annotation indicated that the up-regulated mRNA was enriched in 17 pathways including adherens junction, mTOR signaling pathway, insulin signaling pathway, mitophagy, tight junction, PPAR signaling pathway and TNF signaling pathway, etc. Meanwhile, the down-regulated mRNA was gathered in AMPK signaling pathway, metabolism of xenobiotics by cytochrome P450, apelin signaling pathway, PPAR signaling pathway, PI3K-Akt signaling pathway, insulin signaling pathway, cardiac muscle contraction, adrenergic signaling in cardiomyocytes, Fc gamma R-mediated phagocytosis, etc. The great potential exhibited by FVP could make it an ideal candidate as complementary medicine or functional food for promotion of health.

A series of steroidal compounds based on 3-hydroxyandrosta-5,7-diene-17-carboxylic acid core structure were designed, synthesized and bio-evaluated for their anti-inflammatory potency. Among them, compound 5c, 6f, and 6q effectively inhibited the production of nitric oxide (NO) in lipopolysaccharide (LPS) stimulated RAW 264.7 macrophages. They inhibited the expression of inducible NO synthase (iNOS) and prostaglandin synthase-2 (COX-2) at mRNA level. Compound 6q displayed inhibitory effects on both iNOS and COX-2 expression in a concentration-dependent manner. Furthermore, 6q was found to effectively decrease the mRNA and protein levels of interleukin 6 (IL-6). Mechanically, 6q could potently downregulate NF-κB signaling via suppression of the Akt/PI3K pathway. Moreover, 6q demonstrated high in vivo anti-inflammatory activities in a mouse colitis model induced by dextran sulfate sodium (DSS). Taken together, these data indicate that 6q represents a novel and promising anti-inflammatory bowel diseases (IBD) agent worthy of further investigation.

Flammulina velutipes polysaccharides (FVP) can improve gut health through gut microbiota and metabolism regulation. In this study, the 28-days fed experiment was used to investigate gut microbime and metabolic profiling induced by FVP. After treatment, intestinal tissue section showed the higher villus height and villus height/crypt depth (V/C) value in FVP-treated group. The 16 s rRNA gene sequencing revealed microbiota composition alteration caused by FVP, as the Firmicutes phylum increased while Bacteroidetes phylum slightly decreased. The metabolic profiling was detected by LC/MS and results showed 56 and 99 compounds were dramatically changed after FVP treatment in positive and negative ion mode, respectively. Annotation in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways displayed the adjustment of energy metabolism, amino acid metabolism, nucleotide metabolism and other related basic pathways after FVP treatment. Our study suggested that FVP can be developed as a dietary supplement for intestine health promotion.

Hydrogels can be used as bioactive dressings, which outperform traditional dressings and are widely used in wound hemostasis and healing. However, it is still a challenge to develop a hydrogel with good stability and strong mechanical properties for wound hemostasis and healing. Herein, we developed a novel composite polysaccharide hydrogel from fenugreek gum and cellulose. Fenugreek gum was combined with cellulose through hydrogen bonding to form a hydrogel to improve the mechanical properties of the composite hydrogel. The composite hydrogel had a porous structure, thermal stability, good water absorption and a sustained release effect. Furthermore, the composite hydrogel demonstrated good biocompatibility in vitro and in vivo. Notably, the superior performance of wound hemostasis and healing has been confirmed. Our results indicated that the composite hydrogel was a promising medical dressing and had the potential to promote wound healing.

Cardiovascular diseases (CVDs), including a series of pathological disorders, severely affect millions of people all over the world. To address this issue, several potential therapies have been developed for treating CVDs, including injectable hydrogels as a minimally invasive method. However, the utilization of injectable hydrogel is a bit restricted recently owing to some limitations, such as transporting the therapeutic agent more accurately to the target site and prolonging their retention locally. This review focuses on the advances in injectable hydrogels for CVD, detailing the types of injectable hydrogels (natural or synthetic), especially that complexed with stem cells, cytokines, nano-chemical particles, exosomes, genetic material including DNA or RNA, etc. Moreover, we summarized the mainly prominent mechanism, based on which injectable hydrogel present excellent treating effect of cardiovascular repair. All in all, it is hopefully that injectable hydrogel-based nanocomposites would be a potential candidate through cardiac repair in CVDs treatment.

Cardiovascular diseases (CVDs) have become a serious threat to human life and health. Though many drugs acting via different mechanism of action are available in the market as conventional formulations for the treatment of CVDs, they are still far from satisfactory due to poor water solubility, low biological efficacy, non-targeting, and drug resistance. Nano-drug delivery systems (NDDSs) provide a new drug delivery method for the treatment of CVDs with the development of nanotechnology, demonstrating great advantages in solving the above problems. Nevertheless, there are some problems about NDDSs need to be addressed, such as cytotoxicity. In this review, the types and targeting strategies of NDDSs were summarized, and the new research progress in the diagnosis and therapy of CVDs in recent years was reviewed. Future prospective for nano-carriers in drug delivery for CVDs includes gene therapy, in order to provide more ideas for the improvement of cardiovascular drugs. In addition, its safety was also discussed in the review.

To ensure the safe use of nanoparticles (NPs) in modern society, it is necessary and urgent to assess the potential toxicity of NPs. Cardiovascular system is required for the systemic distribution of NPs entering circulation. Therefore, the adverse cardiovascular effects of NPs have gained extensive research interests. Metal based NPs, such as TiO2, ZnO and Ag NPs, are among the most popular NPs found in commercially available products. They may also have potential applications in biomedicine, which could increase their contact with cardiovascular systems. This review aimed at providing an overview about the adverse cardiovascular effects of TiO2, ZnO and Ag NPs. We discussed about the bio-distribution of NPs following different exposure routes. We also discussed about the cardiovascular toxicity of TiO2, ZnO and Ag NPs as assessed by in vivo and in vitro models. The possible mechanisms and contribution of physicochemical properties of metal based NPs were also discussed.

Andrographis paniculata Nees is used as a functional food in Japan, Korea, India, and China. Andrographolide, a naturally occurring phytochemical identified in Andrographis paniculata, has been discovered to present anti-inflammatory and anticancer activities. Highly expressed interleukin (IL-8) has been detected in colorectal cancer and is implicated in angiogenesis. However, the effect and molecular mechanisms of IL-8 expression by andrographolide remain obscure in human colorectal cancer cells. The present study was aimed to investigate the effects of andrographolide on TNF-α-induced IL-8 expression and its underlying mechanisms. We found that andrographolide concentration-dependently inhibited TNF-α-induced IL-8 mRNA (2.23 ± 0.15 fold at 20 μM) and protein expression (4.78 ± 0.31 fold at 20 μM) and reduced the IL-8 transcriptional activity (2.59 ± 0.25 fold at 20 μM). TNF-α stimulated the membrane translocation of p47phox to activate reactive oxygen species (ROS)-producing NADPH oxidase (NOX). Furthermore, TNF-α induced Src and MAPKs (Erk1/2, p38 MAPK) phosphorylation, as well as NF-κB and AP-1 binding activities. We found that NF-κB and AP-1 were the critical transcription factors for TNF-α-induced IL-8 expression. Specific inhibitors and mutagenesis studies indicated that Src, Erk1/2, and p38 MAPK are related to TNF-α-induced IL-8. NOX-derived ROS and Src/MAPKs (Erk1/2 and p38 MAPK) functioned as upstream activators of NF-κB and AP-1, respectively. Taken together, andrographolide antagonizes TNF-α-induced IL-8 via inhibition of NADPH oxidase/ROS/NF-κB and Src/MAPKs/AP-1 signaling pathways in HCT116 colorectal cancer cells and then suppresses angiogenesis in the tumor microenvironment.

The flavonoids (POFs) from the leaves of Platycladus orientalis (L.) Franco were purified using six different macroporous adsorption resins including polar resins NKA-9 and ADS-F8, semi-polar resins ADS-17 and AB-8, and non-polar resins D101 and ADS-5. Among semi-polar resins, AB-8 demonstrated the best adsorption and desorption capacities with an adsorption ratio of 86% and a desorption ratio of 52%. According to the Simultaneous Thermogravimetry-Differential Scanning Calorimetry (STA/TG-DSC) analysis, POFs showed three thermally decomposed temperatures (347.6 °C, 437.5 °C and 494.8 °C). The main flavonoids in POFs were identified as esculin, amentoflavone, glabridin, and afromosin. Meanwhile, POFs in the dosage range of 25 to 400 μg mL-1 showed a significant anti-inflammatory effect on lipopolysaccharide (LPS)-induced RAW 264.7 mouse macrophage cells, which could inhibit the secretion of NO, IL-6, and TNF-α through the inhibition of inflammatory-related gene expressions.

International audience; Echinococcosis is a zoonotic infection caused by cestode species of the genus Echinococcus, with limited treatment options. It is urgent to develop new anti-hydatid agent. In this paper, we reported anacardic acid (AA), a natural product isolated from the Brazilian cashew-nut shell liquid, which presented a high activity against metacestodes of Echinococcus multilocularis (E. multilocularis) and Echinococcus granulosus sensu stricto (E. granulosus s.s.) in vitro and in vivo. AA exerted a better efficacy on E. granulosus s.s. protoscoleces and E. multilocularis metacestodes than that of albendazole (ABZ) and dihydroartemisinin (DHA) in vitro, and an inhibition on the growth of Echinococcus metacestode as effective as ABZ in vivo. Moreover, we also found that one of the mechanisms of AA against Echinococcus could be the suppression of angiogenesis on/in the metacestode mass through inhibiting vascular endothelial growth factor (VEGF)—induced signalling pathways. This work finds that AA is a new promising potential candidate drug for echinococcosis treatment.

In the present study, eleven glutathione-derived peptides, including Glu-Cys-His, Pro-Leu-Gly, Pro-Cys-Gly, Phe-Lys-Leu, Leu-His-Gly, Lys-Leu-Glu, Lys-Val-His, Tyr-Glu-Gly, Tyr-His-Leu, Gly-Glu-Leu and Gly-Pro-Glu, were designed. The antioxidant activity of these peptides was investigated by single-electron-transfer (SET) reaction based assays (DPPH radical scavenging ability and reducing power), hydrogen-atom-transfer (HAT) reaction based assays (linoleic autoxidation inhibition activity, ORAC and TEAC) and hydroxyl radical scavenging activity assay. The relationship between the chemical structure and antioxidant activities of the synthetic peptides was analyzed by quantitative structure–activity relationship (QSAR) modeling. Results showed that the amino acids next to C-terminal regions played a much more pivotal role in having high antioxidant activity than those in N-terminal regions. Besides, the difference in free radical category as well as solvent system applied in the antioxidant assay methods could result in different conclusions on the relationship between physicochemical properties (hydrophobicity, steric property and electronic property) and antioxidant activity. The amino acid with high hydrophobic property and steric property in the N-terminal also contributed to the high antioxidant activity of the glutathione-derived peptides.

With lower cell toxicity and higher specificity, novel vaccines have been greatly developed and applied to emerging infectious and chronic diseases. However, due to problems associated with low immunogenicity and complicated processing steps, the development of novel vaccines has been limited. With the rapid development of bio-technologies and material sciences, nanomaterials are playing essential roles in novel vaccine design. Incorporation of nanomaterials is expected to improve delivery efficiency, to increase immunogenicity, and to reduce the administration dosage. The purpose of this review is to discuss the employment of nanomaterials, including polymeric nanoparticles, liposomes, virus-like particles, peptide amphiphiles micelles, peptide nanofibers and microneedle arrays, in vaccine design. Compared to traditional methods, vaccines made from nanomaterials display many appealing benefits, including precise stimulation of immune responses, effective targeting to certain tissue or cells, and desirable biocompatibility. Current research suggests that nanomaterials may improve our approach to the design and delivery of novel vaccines.

The existence of blood-brain barrier (BBB) hampers the effective treatment of central nervous system (CNS) diseases. Almost all macromolecular drugs and more than 98% of small molecule drugs cannot pass the BBB. Therefore, the BBB remains a big challenge for delivery of therapeutics to the central nervous system. With the structural and mechanistic elucidation of the BBB under both physiological and pathological conditions, it is now possible to design delivery systems that could cross the BBB effectively. Because of their advantageous properties, nanoparticles have been widely deployed for brain-targeted delivery. This review paper presents the current understanding of the BBB under physiological and pathological conditions, and summarizes strategies and systems for BBB crossing with a focus on nanoparticle-based drug delivery systems. In summary, with wider applications and broader prospection the treatment of brain targeted therapy, nano-medicines have proved to be more potent, more specific and less toxic than traditional drug therapy.

The urokinase-type plasminogen activator receptor (uPAR), a glycoprotein localized on the cell surface with a glycosylphosphatidylinositol anchor, plays a crucial role in cell invasion, and the metastasis of several cancers, including bladder cancer, and its expression are significantly negatively correlated with patient survival rates. Apigenin, a naturally produced phytochemical compound found in fruits, vegetables, and plant leaves, has been shown to mediate a variety of cancer-metastasis-related molecules in various cancers. The effect of apigenin on uPAR expression is still unknown. In this study, we examined the effects of apigenin on IL-1β-induced uPAR expression and investigated its potential mechanisms. We discovered in this study that IL-1β could remarkably induce uPAR expression in bladder cancer T24 cells and that apigenin-inhibited IL-1β could induce uPAR expression concentration-dependently. Interestingly, NF-κB and AP-1 transcription factors were critically required for IL-1β-induced high uPAR expression. Apigenin suppressed the transcriptional activity of both AP-1 and NF-κB by inhibiting ERK1/2 and JNK signaling pathways. These results suggest that apigenin can exert anti-invasion effects by inhibiting uPAR expression via mediating (ERK1/2, JNK)/AP-1 and (ERK1/2, JNK)/NF-κB signaling pathways in human T24 cells. Our present study generated novel and valuable biological insight into anti-invasion through treatment with a small native compound.

A new water-soluble polysaccharide (FVP1) was extracted from Flammulina velutipes by traditional method “water extraction and alcohol precipitation” and purified by column chromatography. Physicochemical characterization showed that FVP1 was a homogeneous polysaccharide with a relative molecular weight of 54.78 kDa. It is composed of mannose (7.74%), glucose (70.41%), and galactose (16.38%). FVP1 (1000 mg/mL) possessed significant immune activity by increasing the secretion of nitric oxide (NO), tumour necrosis factor-α (TNF-α) (3183 ± 133.84 pg/mL), interleukin (IL)-6 (1133.21 ± 39.05 pg/mL), and IL-12 (579.96 ± 74.53 pg/mL) in macrophages. Furthermore, FVP1 showed significant hepatitis B surface antibody (anti-HBV) activity through reducing the expression of hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg) and hepatitis B virus (HBV) DNA replication. These results suggest a novel role for FVP1 to be applied as an immunomodulators in dietary supplements to prevent HBV infection.

Lots of active substances are hydrophobic materials at ambient and body temperatures, decreasing their bioavailability and posing great challenges to successful incorporation into medication and functional foods. The goal of this research was to develop a nanoemulsion delivery system containing a hydrophobic crystalline bioactive component (nobiletin) to improve the anti-inflammatory activity. Nobiletin was incorporated into the oily phase, and the nanoemulsions were fabricated using high-speed and high-pressure homogenization. Particle size, polydispersity index (PDI), and zeta potential were evaluated by a commercial laser light scattering instrument. The anti-inflammatory activities were performed in LPS-stimulated RAW 264.7 cells. The developed nobiletin nanoemulsion had an average droplet size of 168.6 ± 3.8 nm and a PDI of 0.168, while the average diameter of the blank nanoemulsion was 157.3 ± 1.9 nm and its PDI was 0.161. The zeta potential values of nobiletin nanoemulsion and blank nanoemulsion were -68.45 ± 0.64 and -62.75 ± 0.21 mV, respectively. All obtained nanoemulsions kept physically stable during storage at 4, 25, and 37 °C. A nobiletin-loaded nanoemulsion showed an enhanced anti-inflammatory activity in LPS-induced macrophages, with a decrease in pro-inflammatory mediators and cytokines. The findings suggested that the nanoemulsion would be used as an effective delivery system for nobiletin to improve its anti-inflammatory activity.

A polysaccharide fraction, here called POP1, was purified from the leaves of Platycladus orientalis (L.) Franco by water extraction and alcohol precipitation. Physicochemical characterization indicated that POP1 had a relative molecular weight of 8.10 × 10(3) Da and consisted of rhamnose (5.74%), arabinose (12.58%), mannose (10.97%), glucose (64.96%), and galactose (6.55%). The main linkage types of POP1 consisted of (1→5)-linked α-l-Ara, (1→3)-linked α-l-Man, (1→6)-linked β-l-Rha, (1→4)-linked α-d-Glc, (1→6)-linked α-d-Glc, (1→6)-linked β-d-Gal, (1→3,6)-linked β-d-Gal, and termination with α-l-Man and α-d-Glc residues based on periodate oxidation, Smith degradation, methylation, and NMR analysis. POP1 exhibited excellent immunostimulating activity by enhancing macrophage NO, TNF-α, IL-6, and IL-12 secretion and activating related mRNA expression. Besides, POP1 showed significant anti-HBV activity through inhibiting the expression of HBsAg (IC50 = 1.33 ± 0.12 mg/mL) and HBeAg (IC50 = 1.67 ± 0.13 mg/mL) and interfering with the HBV DNA replication (IC50 = 0.80 ± 0.03 mg/mL). The present study suggested that POP1 could be used as immunoregulatory agent in functional foods for the prevention of HBV infection.

The walnut peptides and zinc ions were combined to generate a walnut peptides-zinc complex (WP1-Zn) with enhanced antiproliferative ability as well as reduced toxicity. The result indicated that Zn ions were successfully combined with WP1 through Zn-N and Zn-O covalent bonds. WP1-Zn compounds exhibited strong antiproliferative ability against the selected human cell lines, especially MCF-7 cells, whose survival rate reduced to 20.02% after exposure to 300 μg/mL of WP1-Zn for 48 h. WP1-Zn inhibited MCF-7 cell proliferation through inducing cell apoptosis and cell cycle arrest. The results indicated that WP1-Zn induced MCF-7 cell apoptosis via the ROS triggered mitochondrial-mediated pathway and cell surface receptor-mediated pathway. Our work is the first attempt to elucidate the synergic effect of novel walnut peptides and Zn and with the hope of better understanding the antiproliferative action of bioactive peptides and a zinc complex and support the potential application of WP1-Zn as a functional food ingredient or complementary medicine.

The protective effects of kaempferol against reactive oxygen species (ROS)-induced hemolysis and its antiproliferative activity on human cancer cells were evaluated in this study. Kaempferol exhibited strong cellular antioxidant ability (CAA) with a CAA value of 59.80 ± 0.379 μM of quercetin (QE)/100 μM (EC50 = 7.74 ± 0.049 μM). Pretreatment with kaempferol significantly attenuated the ROS-induced hemolysis of human erythrocyte (87.4% hemolysis suppressed at 100 μg/mL) and reduced the accumulation of toxic lipid peroxidation product malondialdehyde (MDA). The anti-hemolytic activity of kaempferol was mainly through scavenging excessive ROS and preserving the intrinsic antioxidant enzymes (superoxide dismutase, SOD; catalase, CAT; and glutathione peroxidase, GPx) activities in normal levels. Additionally, kaempferol showed significant antiproliferative activity on a panel of human cancer cell lines including human breast carcinoma (MCF-7) cells, human stomach carcinoma (SGC-7901) cells, human cervical carcinoma (Hela) cells and human lung carcinoma (A549) cells. Kaemperol induced apoptosis of MCF-7 cells accompanied with nuclear condensation and mitochondria dysfunction.

Bio-functionalized nanoparticles with semiconducting/metallic core encapsulated in a bio- or bio-derived materials are promising for applications in biology and especially in cancer diagnostic and healing. In this report, we report a facile, single-step, first-time synthesis and in-situ functionalization strategy for the preparation of monodispersed selenium nanoparticles (SeNPs) functionalized using a novel polysaccharide (DP1) extracted from Dictyophora indusiata (a fungus). The DP1 functionalized SeNPs (DP1-SeNPs), where DP1 is attached to the surface via Se-O bond as well as physic-sorption had, an average diameter of 89 nm and were highly uniform, extremely stable compared to bare SeNPs. Detailed investigation of the biological properties of DP1-SeNP illustrated that they exhibit unprecedented, enhanced and selective antiproliferative activity through inducing cell apoptosis confirmed by nuclear condensation, DNA cleavage and accumulation of S phase cell arrest. The mechanism of the induced apoptosis was found to be a combination of the activation of caspases 3, 8 and 9, the Fas-associated death domain protein (FADD), reactive oxygen species (ROS) overproduction, as well as mitochondrial dysfunction. It is envisioned that the reported DP1-SeNPs will offer a new phase space for high-efficiency anticancer treatment with little side effect.

Wenzhen Liao,1 Rong Zhang,1 Chenbo Dong,2 Zhiqiang Yu,3 Jiaoyan Ren11College of Light Industry and Food Sciences, South China University of Technology, Guangzhou, Guangdong, People’s Republic of China; 2Civil and Environmental Engineering, Rice University, Houston, TX, USA; 3School of Pharmaceutical Science, Guangdong Provincial Key Laboratory of New Drug Screening, Southern Medical University, Guangzhou, Guangdong, People’s Republic of ChinaAbstract: This contribution reports a facile synthesis of degreased walnut peptides (WP1)-functionalized selenium nanoparticles (SeNPs) hybrids with enhanced anticancer activity and a detailed mechanistic evaluation of its superior anticancer activity. Structural and chemical characterizations proved that SeNPs are effectively capped with WP1 via physical absorption, resulting in a stable hybrid structure with an average diameter of 89.22 nm. A panel of selected human cancer cell lines demonstrated high susceptibility toward WP1-SeNPs and displayed significantly reduced proliferative behavior. The as-synthesized WP1-SeNPs exhibited excellent selectivity between cancer cells and normal cells. The targeted induction of apoptosis in human breast adenocarcinoma cells (MCF-7) was confirmed by the accumulation of arrested S-phase cells, nuclear condensation, and DNA breakage. Careful investigations revealed that an extrinsic apoptotic pathway can be attributed to the cell apoptosis and the same was confirmed by activation of the Fas-associated with death domain protein and caspases 3, 8, and 9. In addition, it was also understood that intrinsic apoptotic pathways including reactive oxygen species generation, as well as the reduction in mitochondrial membrane potential, are also involved in the WP1-SeNP-induced apoptosis. This suggested the involvement of multiple apoptosis pathways in the anticancer activity. Our results indicated that WP1-SeNP hybrids with Se core encapsulated in a WP1 shell could be a highly effective method to achieve anticancer synergism. Moreover, the great potential exhibited by WP1-SeNPs could make them an ideal candidate as a chemotherapeutic agent for human cancers, especially for breast cancer.Keywords: selenium nanoparticles, walnut peptides, human cancer cell lines, antiproliferative activity, apoptosis