Effects of solid lipid nanocarrier containing methyl urolithin A by coating folate-bound chitosan and evaluation of its anti-cancer activity.

BACKGROUND: Nanotechnology-based drug delivery systems have received much attention over the past decade. In the present study, we synthesized Methyl Urolithin A-loaded solid lipid nanoparticles decorated with the folic acid-linked chitosan layer called MuSCF-NPs and investigated their effects on cancer cells. METHODS: MuSCF-NPs were prepared using a high-pressure homogenization method and characterized using FTIR, FESEM, DLS, and zeta potential methods. Drug encapsulation was assessed by spectrophotometry and its cytotoxic effect on various cancer cells (MDA-MB231, MCF-7, PANC, AGS, and HepG2) by the MTT method. Antioxidant activity was assessed by the ABTS and DPPH methods, followed by expression of genes involved in oxidative stress and apoptosis by qPCR and flow cytometry. RESULTS: The results showed the formation of monodisperse and stable round nanoparticles with a size of 84.8 nm. The drug loading efficiency in MuSCF-NPs was reported to be 88.6%. MuSCF-NPs exhibited selective cytotoxicity against MDA-MB231 cells (IC50 = 40 µg/mL). Molecular analysis showed a significant increase in the expression of Caspases 3, 8, and 9, indicating that apoptosis was occurring in the treated cells. Moreover, flow cytometry results showed that the treated cells were arrested in his SubG1 phase, confirming the pro-apoptotic effect of the nanoparticles. The results indicate a high antioxidant effect of the nanoparticles with IC50 values ​​of 45 µg/mL and 1500 µg/mL against ABTS and DPPH, respectively. The reduction of catalase gene expression confirmed the pro-oxidant effect of nanoparticles in cancer cells treated at concentrations of 20 and 40 µg/mL. CONCLUSIONS: Therefore, our findings suggest that the MuSCF-NPs are suitable candidates, especially for breast cancer preclinical studies.

The effect of EGCG/tyrosol-loaded chitosan/lecithin nanoparticles on hyperglycemia and hepatic function in streptozotocin-induced diabetic mice.

We aimed to study the potential of epigallocatechin-3-gallate/tyrosol-loaded chitosan/lecithin nanoparticles (EGCG/tyrosol-loaded C/L NPs) in streptozotocin-induced type 2 diabetes mellitus (T2DM) mice. The EGCG/tyrosol-loaded C/L NPs were created using the self-assembly method. Dynamic light scattering, Field Emission Scanning Electron Microscopy, and Fourier transform infrared spectroscopy were utilized to characterize the nanoparticle. Furthermore, in streptozotocin-induced T2DM mice, treatment with EGCG/tyrosol-loaded C/L NPs on fasting blood sugar levels, the expression of PCK1 and G6Pase, and IL-1ß in the liver, liver glutathione content, nanoparticle toxicity on liver cells, and liver reactive oxygen species were measured. Our findings showed that EGCG/tyrosol-loaded C/L NPs had a uniform size distribution, and encapsulation efficiencies of 84 % and 89.1 % for tyrosol and EGCG, respectively. The nanoparticles inhibited PANC-1 cells without affecting normal HFF cells. Furthermore, EGCG/tyrosol-loaded C/L NP treatment reduced fasting blood sugar levels, elevated hepatic glutathione levels, enhanced liver cell viability, and decreased reactive oxygen species levels in diabetic mice. The expression of gluconeogenesis-related genes (PCK1 and G6 Pase) and the inflammatory gene IL-1ß was downregulated by EGCG/tyrosol-loaded C/L NPs. In conclusion, the EGCG/tyrosol-loaded C/L NPs reduced hyperglycemia, oxidative stress, and inflammation in diabetic mice. These findings suggest that EGCG/tyrosol-loaded C/L NPs could be a promising therapeutic option for type 2 diabetes management.

Preparation of the Myricetin-Loaded PEGylated Niosomes and Evaluation of their in†vitro Anti-Cancer Potentials.

Several edible plants contain flavonoids, including myricetin (Myr), which perform a wide range of biological activities. Myr has antitumor properties against various tumor cells. In this study Myr-loaded PEGylated niosomes (Myr-PN) were prepared and their anti-cancer activities were evaluated in vitro. Myr-PNs were prepared as a tool for drug delivery to the tumor site. Myr-PN was characterized in terms of size, zeta potential, and functional groups using dynamic light scattering (DLS), Fourier-transform infrared spectroscopy (FTIR), and field emission scanning electron microscopy (SEM). The Myr-PN size was 241 nm with a polydispersity index (PDI) of 0.20, and zeta potential -32.7±6.6 mV. Apoptotic properties of Myr-PN against normal and cancer cell lines were determined by flow cytometry and real-time quantitative PCR. Cancer cells showed higher cytotoxicity when treated with Myr-PN compared with normal cells, indicating that the synthesized nanoparticles pose no adverse effects. Apoptosis was induced in cells treated with 250 µg/mL of Myr-PN, in which 45.2 % of cells were arrested in subG1, suggesting that Myr-PN can induce apoptosis. In vitro, the synthesized Myr-PN demonstrated potent anticancer properties. Furthermore, more research should be conducted in vitro and in vivo to study the more details of Myr-PN anti-cancer effects.

Nanoformulated meloxicam and rifampin: inhibiting quorum sensing and biofilm formation in Pseudomonas aeruginosa.

Background: We aimed to investigate the simultaneous effects of meloxicam and rifampin nanoformulations with solid lipid nanoparticle (SLN) and nanostructured lipid carrier (NLC) substrates on inhibiting the quorum-sensing system of Pseudomonas aeruginosa and preventing biofilm formation by this bacterium. Methods: Antimicrobial activity of rifampin and meloxicam encapsulated with SLNs and NLCs against P. aeruginosa PAO1 was assessed by disk diffusion, minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). Results: The SLN formulation was associated with lower doses for the MIC and minimum bactericidal concentration in comparison to NLC. Moreover, our results demonstrated that both nanoformulations were able to produce 100% inhibition of the biofilm formation of P. aeruginosa PAO1. Conclusion: All these findings suggest that meloxicam and rifampin encapsulated with SLNs could be the most effective formulation against P. aeruginosa.

Novel formulation of parthenolide-loaded liposome coated with chitosan and evaluation of its potential anticancer effects in vitro.

BACKGROUND: In this study the formulation of parthenolide (PN), an anticancer agent extracted from a natural product, into a liposome (PN-liposome), was examined. The surface of the PN-liposome was modified using chitosan (PN-chitosome). By using real-time quantitative PCR and flow cytometry, we examined the release of PN-chitosomes, cytotoxicity, and ability to induce apoptosis in vitro. METHODS AND RESULTS: According to the present study, PN-chitosomes had a size of 251 nm which is acceptable for efficient enhanced permeation and retention (EPR) performance. PN-chitosomes were confirmed to be spherical in shape and size through FESEM analysis. In terms of encapsulation efficiency, 94.5% was achieved. PN-chitosome possessed a zeta potential of 34.72 mV, which was suitable for its stability. According to the FTIR spectra of PN and PN-chitosome, PN was chemically stable due to the intermolecular interaction between the liposome and the drug. After 48 h, only 10% of the PN was released from the PN-chitosome in PBS (pH 7.4), and less than 20% was released after 144 h. CONCLUSION: In a dose-dependent manner, PN-chitosome exhibited anticancer properties that were more cytotoxic against cancer cells than normal cells. Moreover, the formulation activated both the apoptosis pathway and cytotoxic genes in real-time qPCR experiments. According to the cytotoxicity and activating apoptosis of the prepared modified particle, PN-chitosome may be helpful in the treatment of cancer.

Anti-Cancer and Anti-Oxidant Effects of Fenoferin-loaded Human Serum Albumin Nanoparticles Coated with Folic Acid-bound Chitosan.

BACKGROUND: Several diseases, including cancer, can be effectively treated by altering the nanocarrier surfaces so that they are more likely to be targeted. OBJECTIVE: This study aimed to prepare human albumin (HSA) nanoparticles containing Fenoferin (FN) modified with folic acid (FA) attached to Chitosan (CS) to improve its anti-cancer properties. METHODS: Nanoparticles were first synthesized and surface modified. Their physicochemical properties were assessed by different methods, such as FESEM, FTIR, and DLS. In addition, the percentage of drug encapsulated was measured by indirect method. Besides evaluating the cytotoxic effects of nanoparticles using the MTT assay, the antioxidant capacity of FN-HSA-CS-FA was assessed using the ABTS and DPPH methods. Nanoparticles were also investigated for their anti-cancer effects by evaluating the expression of apoptosis and metastasis genes. RESULTS: Based on this study, FN-HSA-CS-FA was 165.46 nm in size, and a uniform dispersion distribution was identified. Particles were reported to have a zeta potential of +29 mV, which is within the range of stable nanoparticles. Approximately 75% of FN is encapsulated in nanoparticles. Cytotoxic assay determined that liver cancer cells were most sensitive to treatment with an IC50 of 144 µg/ml. Inhibition of free radicals by nanoparticles is estimated to have an IC50 value of 195.23 and 964 µg/ml, for ABTS and DPPH, respectively. In the treatment with nanoparticles, flow cytometry results of arresting the cells in the SubG1 phase and real-time qPCR results indicated increased expression of caspases-3, caspase-8, and caspase-9 genes. CONCLUSION: According to this study, synthesized nanoparticles inhibited free radicals and activated apoptosis in liver cancer cells, and the capability of these nanoparticles to inhibit cancer cells was also confirmed. This formulation can, therefore, be used in preclinical studies to test the efficacy of the drug.

The Combinational Effect of Inulin and Resveratrol on the Oxidative Stress and Inflammation Level in a Rat Model of Diabetic Nephropathy.

Background: Using inulin can enhance resveratrol's effects by improving the intestinal microbiome and the stability of resveratrol. Objectives: We aimed to investigate the effect of therapeutic intervention with combined inulin and resveratrol on kidney function in diabetic rats. Methods: Diabetic model was induced by intraperitoneal injection of streptozotocin. Afterward, rats were divided into 6 groups: control, diabetic without treatment, diabetic treated with insulin, diabetic treated with resveratrol, diabetic treated with inulin, and diabetic treated with a combination of inulin and resveratrol. After 10 wk, the creatinine, urea, insulin, urinary proteins, and inflammatory and oxidative stress markers were evaluated. Pathologic changes were examined in kidney tissues. Results: Renal dysfunction, accompanied by increased inflammation and oxidative stress, was observed. Our results showed that treatment with resveratrol and inulin had antidiabetic effects and was associated with reduced renal dysfunction, oxidative stress, and kidney inflammation. In addition, it was observed that combined treatment with inulin and resveratrol outperformed monotherapies in improving kidney function and reducing oxidative stress and inflammation. Conclusions: Treatment with resveratrol and inulin can have renoprotective effects by improving oxidative stress and inflammation in kidney tissues. Therefore, employing these 2 compounds is suggested as an inexpensive and available method for diabetic nephropathy.

Evaluation of the effect of designed PLGA-arctiin nanoparticles modified with folic acid and chitosan on colon cancer cells.

In this study, we designed nanoparticles (NPs) based on polylactic acid glycolic acid modified with chitosan and folic acid to optimize the anti-cancer, anti-inflammatory, and antioxidant effects of arctiin (ARC), and we measured its effects on cancer cells, including colon cancer. NPs were synthesized using the W1/O/W2 double-emulsion solvent evaporation method. Physicochemical characteristics of synthesized NPs (ARC-PCF-NPs), including average particle size, dispersity index (PDI), zeta potential (ZP), field emission scanning electron microscope figures, and encapsulation efficiency (EE), were evaluated. 2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and ferric reducing antioxidant power (FRAP) methods were carried out to determine the antioxidant properties of NPs. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay was performed to investigate cytotoxicity effects on cancer cells and normal fibroblasts. Quantitative polymerase chain reaction was also performed on inflammatory and antioxidant genes. The obtained results indicated that the synthesized NPs have a size of 100 nm, a DPI of 0.36, a ZP of 26.30 mV, and EE was calculated at about 87.5%. The antioxidant influence of ARC-PCF-NPs was confirmed by inhibiting ABTS and DPPH free radicals and ferrous reduction in the FRAP method. Moreover, the reduction of inflammatory and antioxidant genes confirmed the anti-inflammatory and antioxidant properties of NPs. These results indicate the modification of the surface of NPs in order to increase the bioavailability, stability, and effectiveness of medicinal compounds in therapeutic applications.

Study the Anticancer Properties of Thymol-Loaded PEGylated Bovine Serum Albumin Nanoparticles Conjugated with Folic Acid.

Phenolic compounds such as Thymol have an effective role in suppressing cancer, however, their low solubility in aqueous solution has limited their use. This study aimed to prepare Thymol (TY)-loaded bovine serum albumin (BSA) nanoparticles surface-modified with polyethylene glycol (PEG) conjugated with folic acid (FA) and evaluate their inhibitory activity on cancer cells. The TY-BSA-PEG-FA was characterized using DLS, FESEM, and FTIR. The encapsulation efficiency (EE) was evaluated indirectly by using UV absorption. The antioxidant property of nanoparticles was evaluated by 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and ferric reducing ability of plasm (FRAP) methods. The effects of nanoparticles against cancer cells were investigated by MTT, AO/PI, flow cytometry, and real-time qPCR methods. The results showed the spherical morphology of TY-BSA-PEG-FA with an average size of 70.0 nm, a PDI of 0.32, a zeta potential of -11.3 mV, and an EE of 89.0±2.3 %. The cytotoxicity effects of nanoparticles against all cell lines were in a concentration-dependent manner. AGS gastric cancer cells were reported to be the most vulnerable to treatment, while pancreatic cancer cells (PANC-1) and normal skin cells (HFF) would be the most resistant. The SubG1 phase arrest of about 66 % occurred at 85 µg/mL. An increase in apoptotic cells in fluorescent staining, along with decreased expression of Bcl-2 and increased expression of the BAX gene demonstrated the induction of apoptosis in treated cells. The powerful inhibitory effect of nanoparticles in inhibiting ABTS free radicals (IC50 =82 µg/mL) and DPPH free radicals (IC50 =844 µg/mL) and the ability to reduce iron ions indicated the antioxidant effects of TY-BSA-PEG-FA. Based on these results, the synthesized nanoparticles may be suitable for further investigation in the treatment of cancer, notably gastric cancer.

The Effects of Resveratrol Supplementation on the Metabolism of Lipids in Metabolic Disorders.

Lipids are stored energy sources in animals, and disturbance of lipid metabolism is associated with metabolic disorders, including cardiovascular diseases, obesity, nonalcoholic fatty liver disease, and diabetes. Modifying dysregulated lipid metabolism homeostasis can lead to enhanced therapeutic benefits, such as the use of statin therapy in cardiovascular disease. However, many natural compounds may have therapeutic utility to improve lipid metabolism. Resveratrol is a polyphenol extracted from dietary botanicals, including grapes and berries, which has been reported to affect many biological processes, including lipid metabolism. This review evaluates the effects of resveratrol on lipid metabolism dysregulation affecting atherosclerosis, diabetes, and nonalcoholic fatty liver disease (NAFLD). In addition, it details the mechanisms by which resveratrol may improve lipid metabolism homeostasis.

Preparation and Characterization of Allicin-Loaded Solid Lipid Nanoparticles Surface-Functionalized with Folic Acid-Bonded Chitosan: In Vitro Anticancer and Antioxidant Activities.

OBJECTIVE: This investigation aimed to increase the bioavailability and anticancer effects of allicin (AC) by encapsulating it in solid lipid nanoparticles (SLN) decorated with chitosan (CS)-conjugated folic acid (FA). MATERIAL AND METHODS: Nanoparticles (NPs) were synthesized by high-pressure homogenization, and then, Fourier-transform infrared (FTIR), Field-Emission Scanning Electron Microscopy (FESEM), Dynamic Light Scattering (DLS), and zeta potential methods were used to determine their physicochemical characteristics. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed to assess the effect of toxicity and flow cytometry, while fluorescent staining methods were used to investigate the type of cell death. Real-time quantitative polymerase chain reaction (qPCR) was used to evaluate the expression levels of apoptotic genes: Bcl-2, and caspase-8. RESULTS: The presence of AC-SLN-CS-FA with a spherical morphology, an average size of 86.7 ± 9.4 nm, uniform distribution (0.31), a surface charge of +21.3 ± 13.3 mV, an encapsulation percentage of 86.3%, and a folate binding rate of 63% confirmed the success of the preparation method. Suppression of MCF-7 cancer cells and non-toxicity of AC-SLN-CS-FA on Human foreskin fibroblast (HFF) normal cells were confirmed by cytotoxic assay. The results of flow cytometry revealed that the cells were arrested in the sub-G1 phase, and the activation of the intrinsic apoptosis pathway was confirmed by the results of real-time qPCR. CONCLUSIONS: In general, AC-SLN-CS-FA has the potential to prevent free radicals and trigger apoptosis in cancer cells by activating the intrinsic apoptosis pathway; thus, making it a promising subject in preclinical research.

PEGylated Lecithin-Chitosan-Folic Acid Nanoparticles as Nanocarriers of Allicin for In Vitro Controlled Release and Anticancer Effects.

In this study, chitosan-lecithin nanoparticles modified with polyethylene glycol (PEG) and folic acid (FA) were used to deliver allicin (AC) to colon cancer cells. AC-loaded polyethylene glycol (PEG) and folic acid (FA)-modified chitosan-lecithin nanoparticles (AC-PLCF-NPs) were fabricated via self-assembling procedure. HPLC for AC encapsulation and FA binding, MTT for viability assay, ABTS and DPPH for antioxidant capacity, disc diffusion, MIC and MBC for antibacterial assay, qPCR and AO/PI staining for apoptotic, and CAM assay for angiogenesis effects of AC-PLCF-NPs were used. AC-PLCF-NPs (113.55 nm) were synthesized as single dispersed (PDI: 0.28) and stable (ZP: + 33.18 mV) with 81% AC encapsulation and 48% FA binding. The antioxidant power of AC-PLCF-NPs was confirmed by inhibiting free radicals ABTS (74.25 µg/mL) and DPPH (366.214 µg/mL) and its antibacterial capacity with very high inhibitory effects against gram-negative bacterial strains. MTT results showed higher toxicity of AC-PLCF-NPs (68.06 µg/mL) compared to AC (171.45 µg/mL). Increased expression of caspase 3 and 9 genes showed activation of the intrinsic apoptosis pathway in treated cells, and on the other hand, reduction of vascular and embryonic growth factors in CAM model confirmed the anti-angiogenesis effects of AC-PLCF-NPs. AC-PLCF-NPs can be suggested as a promising therapeutic agent for studies in the field of colon cancer treatment.

Fabrication of bovine serum albumin-polyethylene glycol nanoparticle conjugated-folic acid loaded-naringenin as an efficient carrier biomacromolecule for suppression of cancer cells.

Flavonoid compounds play an effective role in cancer suppression and today nanocarriers play an important role in improving the physicochemical properties and transmission of these compounds. In this study, polyethylene glycol-modified albumin nanoparticles were synthesized by desolvation method; after loading of naringenin (NRG), folic acid (FA) binding to the surface of nanoparticles was performed (BSA-PEG-FA-NG-NPs). The extent of NRG trapping and FA binding was assessed indirectly using UV absorption methods. The physicochemical properties of BSA-PEG-FA-NG-NPs were investigated by DLS, SEM electron microscopy, and FTIR methods, after which their effects were evaluated on the apoptosis mechanism via MTT, flow cytometry, and qPCR methods. The BSA-PEG-FA-NG-NPs with spherical morphology had dimensions of 205 nm with zeta-potential of 20.61 mV and dispersion index of 0.36. The NRG encapsulation was 84% and the FA binding was 75%. Anticancer effects of BSA-PEG-FA-NG-NPs were confirmed based on inhibiting breast cancer cells (IC50: 922 µg/ml), cell cycle arrest (SubG1 phase), and induction of apoptosis (upregulation of Caspase 3, 8, and 9).

PEGylated Lecithin-Chitosan Nanoparticle-Encapsulated Alphα-Terpineol for In Vitro Anticancer Effects.

The aim of this study was to fabrication PEGylated lecithin-chitosan nanoparticles (PLC-NPs) as alphα-Terpineol's (αT-PLC-NPs) delivery system and examine its anti-cancer effects. αT-PLC-NPs were synthesized by self-assembling method; after characterization, entrapment efficiency of α-T was measured by HPLC procedure. MTT test was conducted for cytotoxicity evaluation. Chick chorioallantoic membrane (CAM) and quantitative polymerase chain reaction (qPCR) analysis were used to determine the angiogenesis properties, and qPCR, flow cytometry, and acridine orange and propidium iodide (AO/PI) staining were used to evaluate the pro-apoptotic effects of αT-PLC-NPs. Finally, the anti-inflammatory and antibacterial activity of the αT-PLC-NPs was also evaluated. αT-PLC-NPs with a size of 220.8 nm, polydispersity index (PDI) of 0.3, zeta potential of +29.03 mV, and encapsulation efficiency of 82% showed higher inhibitory effect on MCF7 cells (IC50: 750 µg/mL) compared to HFF cells (above 1000 µg/mL). Decreased angiogenesis indices and embryonic growth factors in CAM assay, decreased expression of VEGF and VEGF-R genes, and decreased cell migration showed the inhibitory effect of αT-PLC-NPs on angiogenesis. Increased expression of P53, P21, and caspase9 genes, as well as the results of AO/PI staining along with increasing the number of SubG1 phase cells in flow cytometry, confirmed the pro-apoptotic effects of αT-PLC-NPs. Also, its anti-inflammatory effects were demonstrated by inhibiting the expression of pro-inflammatory cytokines (TNF-α and IL-6). The inhibitory power of αT-PLC-NPs in suppressing gram-positive and negative bacterial strains was demonstrated by disk diffusion (DD), minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC) methods. PLC-NPs are a promising carrier for α-T transfer for preclinical studies.

The Brassica Napus Extract (BNE)-Loaded PLGA Nanoparticles as an Early Necroptosis and Late Apoptosis Inducer in Human MCF-7 Breast Cancer Cells.

Loading of the Brassica napus extract (BNE) on PLGA nanoparticle (BNE-PNP) and study its necroptotic activity in human MCF7-breast cancer cells. Double emulsion solvent evaporation methods were used for synthesis of BNE-PNP and DLS, SEM, and surface Zeta-potential analysis were applied for defining the physicochemical properties of BNE-PNP. The cytotoxic impact of BNE-PNP nanoparticles was analyzed by MTT assay and expression of apoptotic (P53 and Cas-3) and necrotic (TNF-α) gene markers were measured by qPCR to evaluate the BNE-PNP-induced cell death type. The stable (-36.07 mV) BNE-PNP were synthesized at 71.07 nm dimension. They significantly decrease the count of metabolically active MCF7 cells (IC50: 170.94 µg/ml after 48 h). The BNE-PNP induced an early programmed necrotic (necroptosis) and late apoptotic death on the MCF7 cancer cells by up-regulating all the P53/TNF-α and Cas-3 gene expression, respectively. The BNE-PNP dose-dependently induced an early cell-selective necroptotic death. Since the necroptotic death is known as a biocompatible cellular death induction, the BNE-PNP have the potential to be used as a safe efficient anticancer compound.

Teucrium polium extract-loaded solid lipid nanoparticles: A design and in vitro anticancer study.

Teucrium polium extract (TPE) is a natural product with potent anticancer activity because of its terpenoid and flavonoid content. The aim of this study was to synthesize solid lipid nanoparticles (SLN) containing T. polium extract (TPE-SLNs) and to evaluate its anti-cancer effect. Formulations of TPE-SLNs were prepared using high-shear homogenization followed by the ultra-sonication technique. Then the TPE-SLNs were characterized by dynamic light scattering (DLS), Zetasizer and field-emission scanning electron microscopy (FESEM), and Fourier transform infrared spectroscopy methods. After confirming the presence of nanoparticles, its anti-proliferative activity was evaluated on Ntra-2 cancer cells and compared to human foreskin fibroblasts (HFF) as a normal cell line by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The pro-apoptotic (flow cytometry) and quantitative PCR (qPCR) and anti-angiogenic (chick chorioallantoic membrane (CAM)) and anti-inflammatory (qPCR) effects of TPE-SLNs were assessed by various methods. TPE-SLNs (85.5 nm, PDI: 0.39, and zeta potential: -25.5 mv) were inhibited by the proliferation of Ntra-2 cancer cells with half-maximal inhibitory concentration (IC50 ; 106.58 µg/ml). Moreover, by increasing the expression of caspase-3,9 and decreasing the expression of interleukin 6 (IL-6), IL-1b, and Bcl-2 genes, apoptosis and anti-inflammatory effects were observed. Reduction of angiogenesis was observed by the reduction of genes involved in angiogenesis and reduction of vascular and embryonic factors in the CAM assay. Activation of various mechanisms of inhibiting cancer cells in the treatment of nanoparticles was demonstrated in the present study. Therefore, these nanoparticles can be recommended for therapeutic purposes. PRACTICAL APPLICATIONS: Solid lipid nanoparticles (SLNs) are composed of pure solid fats and have been researched for many applications. Advantages such as high safety, low toxicity, control of drug release, and increase in chemical stability of loaded drugs distinguish these systems from other colloidal systems. According to the results of this study, solid lipid nanoparticles (SLN) containing T. polium extract showed their anti-cancer effects through various strategies such as inhibiting angiogenesis, inhibiting inflammation, and inducing apoptosis on Ntra-2 cells. These results make it possible to apply these nanocarriers in the loading and transport of drugs to treat various diseases such as cancer.

The Apoptotic, Cytotoxic, and Antiangiogenic Impact of Linum usitatissimum Seed Essential Oil Nanoemulsions on the Human Ovarian Cancer Cell Line A2780.

BACKGROUND: Linum usitatissimum seed essential oil (LSEO) has been used to reduce the risk of prostate and colon cancer. In this study, we optimized the bio-accessibility and bio-compatibility of LSEO to evaluate its cytotoxic, apoptotic and anti-angiogenic impact on the human ovarian cancer cell line A2780. METHOD: We produced LSEO nanoemulsions (LSEO-NEs) utilizing the ultrasound-based technique and the size, its droplets' morphology and stability were characterized. LSEO-NE cytotoxicity was studied by estimating the viability of A2780 human ovarian cancer cell and normal human foreskin fibroblasts (HFFS). Their apoptotic activity was evaluated measuring the Caspase-3, 8 and nine gene expression. Finally, its anti-angiogenic potential was measured applying Chick Chorioallantoic Membrane (CAM) assay. RESULTS: A significant dose-dependent cytotoxic impact of LSEO-NE was detected in the A2780 cells and not in HFF cellsThe apoptotic genes expression profile confirmed the A2780 cell apoptosis death. Moreover, the reduction in length and number of blood vessels in the CAM assay demonstrated the anti-angiogenic activity of LSEO-NE. CONCLUSION: The cancer cell-selective cytotoxicity apoptosis, and anti-angiogenic effects of LSEO-NE indicate its potential as a novel anticancer compound. However, further cell lines have to be analyzed in case of its potential anticancer impacts on human ovarian cancer cells.

The Arachis hypogaea Essential Oil Nanoemulsion as an Efficient Safe Apoptosis Inducer in Human Lung Cancer Cells (A549).

Nanoemulsions have improved therapeutic efficiency. In this regard, due to the Arachis hypogaea components such as flavonoids, we planned to produce Arachis hypogaea oil nanoemulsion (AHO-NE) in order to evaluate its anticancer impacts on A549 lung cancer cells.  The AHO-NE was formulated by ultrasonication, characterized, and used in treating A549 cells. Then, we evaluated Caspase-3 gene expression, flow cytometry results, and MTT assay on A549 cells to check its anticancer impacts. The 50.3 nm AHO-NE significantly reduced the of A549 cells' viability comparing with HFF normal cells. The increasing SubG1 peaks and Cas3 overexpression indicate the AHO-NE apoptotic impact on A549 cells. We found its antioxidant activity (ABTS IC50 = 270.42 µg/ml and DPPH IC50 = 208.51 µg/ml). In conclusion, AHO-NE has the potential to be used as an exclusive cell-dependent anticancer compound in A549 lung cancer cells.

PLGA-Based Nano-Encapsulation of Trachyspermum Ammi Seed Essential Oil (TSEO-PNP) as a Safe, Natural, Efficient, Anticancer Compound in Human HT-29 Colon Cancer Cell Line.

Colorectal cancer is a lethal and commonly diagnosed cancer worldwide. To halt its burden more efficient targeted strategies are needed. Trachyspermum ammi seed essential oil (TSEO) contains several anticancer phytochemicals that maybe more effective via PLGA-based nano-encapsulation. TSEO-PNP nanoparticles were synthesized utilizing evaporation and ultra-sonication-based emulsification methods. Their size, morphology, and stability were defined by DLS, SEM, and surface zeta-potential data, respectively. The TSEO-PNP antioxidant apoptotic, cytotoxic, and antiangiogenic impacts on both cell lines (HT-29 and HUVEC) were studied by FRAP/ABTS, Q-PCR, MTT, and CAM assays, respectively. Moreover, further confirmatory measurements such as AO/EB fluorescent staining and flow cytometry analysis were performed to verify apoptosis. Stable (-32.42 mV) 206.21-nm TSEO-PNP induced apoptosis in the HT-29 cells. Apoptosis was confirmed by significant overexpression of apoptotic genes (Cas-9 and BAX), down-regulation of the anti-apoptotic (BCL-2) gene, fluorescent AO/EB staining, and flow cytometry data following increased TSEO-PNP treatment doses. TSEO-PNP exhibited a meaningful dose- and time-dependent cancer-specific cytotoxic impact on HT-29 cells. The TSEO-PNP has three main anticancer activities on HT-29 colon cancer cells including oxidant reduction, apoptosis induction, and angiogenesis suppression.

Producing the sour cherry pit oil nanoemulsion and evaluation of its anti-cancer effects on both breast cancer murine model and MCF-7 cell line.

Aims: The sour cherry pit oil (SCPO) displays the potent anti-inflammatory, and antioxidant activities. In the present study, we have produced the SCPO nanoemulsion (SCPO-NE) to evaluate their anticancer impacts on breast cancer comparing with its un-processed oil. Methods: We employed an ultrasonication method to formulate the stable SCPO-NE. Their size, stability, and morphology were measured. Then, their cytotoxic impacts and apoptotic activity were checked on MCF7 breast cancer cells and compared with the normal Human foreskin fibroblasts (HFF). Finally, their anti-tumour effect was studied on murine breast cancer model (inoculated with TUBO cancer cells). Results: The results indicated the 36.5 nm stable SCPO-NE significantly decreased the MCF7 cells viability comparing with normal HFF cells, and reduced the tumour size in the murine model. Conclusion: We suggest that SCPO-NEs are able to efficiently inhibit breast cancer progression in both MCF7 cells and murine breast cancer model through apoptotic death induction.