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.

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.

Synthesis and evaluation of biological effects of modified graphene oxide nanoparticles containing Lawson (Henna extract) on gastric cancer cells.

PURPOSE: Targeted Graphene Oxide (GO) nanoparticles can play an important role in the treatment of cancer by increasing cancer cell targeting. This study was conducted to synthesize GO nanoparticles functionalized with chitosan-folate (CS-FA) to deliver a natural product Lawsone (LA) for cancer treatment. METHODS: After characterization of the LA-GO-CS-FA, antioxidant activities of the nanoparticles were investigated by ABTS, DPPH, and FRAP tests. CAM assay was used to study the effect of nanoparticles on angiogenesis. The expression level of inflammatory and angiogenic genes in cells treated with nanoparticles was evaluated by real-time PCR. RESULTS: The findings demonstrated the formation of nanoparticles with a size of 113.3 nm, a PDI of 0.31, and a surface charge of + 11.07 mV. The percentages of encapsulation efficiency were reported at 93%. Gastric cancer cells were reported as the most sensitive to treatment compared to the control, and the gastric cancer cells were used to study gene expression changes. The anti-angiogenic effects of nanoparticles were confirmed by reducing the average number and length of blood vessels and reducing the height and weight of embryos in the CAM assay. The reducing the expression of genes involved in angiogenesis in real-time PCR was demonstrated. Nanoparticles displayed high antioxidant properties by inhibiting DPPH and ABTS radicals and reducing iron ions in the FRAP method. The reduction of pro-inflammatory genes in AGS cells which were treated with nanoparticles indicates the anti-inflammatory properties of nanoparticles. CONCLUSION: This study showed the efficacy of nanoparticles in inhibiting gastric cancer cells by relying on inhibiting angiogenesis.

Synthesis Folate-linked Chitosan-coated Quetiapine/BSA Nano-Carriers as the Efficient Targeted Anti-Cancer Drug Delivery System.

Quetiapine (QTP) has been known to suppress cancer progression in patients suffering from mental disorders. This study aimed to produce the folate-linked chitosan-coated quetiapine/BSA nano-carriers (FCQB-NCs) and evaluate their antioxidant, apoptotic, and anti-metastatic potentials on prostate, pancreas, colon, and breast cancer cell lines. The FCQB-NCs were designed, produced, and characterized using DLS, FESEM, FTIR, and Zeta potential techniques. The nano-carriers antioxidant activity was studied by applying ABTS, DPPH, and FRAP assays. The FCQB-NCs' cytotoxicity and apoptotic/metastatic properties were evaluated utilizing MTT assay and qPCR-based analysis for measuring the apoptotic (Nf-KB)/metastatic (MMP2, MMP9, and MMP13) gene expression, respectively. The AO/PI fluorescent cell staining, DAPI staining, and scratch assay methods were conducted to verify the apoptotic and anti-metastatic activities of FCQB-NCs. The 51-nm FCQB-NCs (PDI = 0.26) exhibited antioxidant activity and selectively decreased the MDA-MB-231 cancer cells' viability by inducing Nf-KB overexpression, which caused the apoptosis pathway activation. Moreover, the FCQB-NCs suppressed the MDA-MB-231 cells' metastatic activity by down-regulating the MMP2, MMP9, and MMP13 gene expression, verified by detecting the decreased migration rate. The FCQB-NCs selectively induced apoptosis and suppressed metastasis in the human breast cancer cell line, which can be attributed to the stepwise release of QTP in two primary (extra-cellular release) and secondary (intra-cellular release) phases. The efficient selective cytotoxic impact of FCQB-NCs can be due to the novel stepwise release mechanism of the FCQB-NCs based on the two-phase entrapment of QTP by BSA and chitosan molecules. Therefore, FCQB-NCs have the potential to be used as an efficient selective anti-breast cancer.

Enhancement of exopolysaccharide production from Ganoderma lucidum using a novel submerged volatile co-culture system.

Based on the impact of volatile organic compounds (VOCs) on secondary metabolite pathways, a novel submerged volatile co-culture system was constructed, and the effects of thirteen fungal and bacterial VOCs were investigated on Ganoderma lucidum exopolysaccharides production. The results demonstrated at least a 2.2-fold increase in exopolysaccharide (EPS) specific production yield in 6 days submerged volatile co-culture of G. lucidum with Pleurotus ostreatus. Therefore, P. ostreatus was selected as a variable culture, and the effects of agitation speed, inoculum size, initial pH, and co-culture volume on EPSs production were investigated using a Taguchi L9 orthogonal array. Finally, the highest concentration of EPSs (3.35 ± 0.22 g L-1) was obtained under optimized conditions; initial pH 5.0, inoculum size 10%, 150 rpm, and 3:1 volume ratio of variable culture to main culture.

Biodesulfurization of dibenzothiophene by a newly isolated Rhodococcus erythropolis strain.

A new dibenzothiophene (DBT) desulfurizing bacterium was isolated from oil-contaminated soils in Iran. HPLC analysis and PCR-based detection of the presence of the DBT desulfurization genes (dszA, dszB and dszC) indicate that this strain converts DBT to 2-hydroxybiphenyl (2-HBP) via the 4S pathway. The strain, identified as Rhodococcus erythropolis SHT87, can utilize DBT, dibenzothiophene sulfone, thiophene, 2-methylthiophene and dimethylsulfoxide as a sole sulfur source for growth at 30 degrees C. The maximum specific desulfurization activity of strain SHT87 resting cells in aqueous and biphasic organic-aqueous systems at 30 degrees C was determined to be 0.36 and 0.47 micromol 2-HBP min(-1) (gdrycell)(-1), respectively. Three mM DBT was completely metabolized by SHT87 resting cells in the aqueous and biphasic systems within 10h. The rate and the extent of the desulfurization reaction by strain SHT87 suggest that this strain can be used for the biodesulfurization of diesel oils.