Combinational therapy with Myc decoy oligodeoxynucleotides encapsulated in nanocarrier and X-irradiation on breast cancer cells.

The Myc gene is the essential oncogene in triple-negative breast cancer (TNBC). This study investigates the synergistic effects of combining Myc decoy oligodeoxynucleotides-encapsulated niosomes-selenium hybrid nanocarriers with X-irradiation exposure on the MDA-MB-468 cell line. Decoy and scramble ODNs for Myc transcription factor were designed and synthesized based on promoter sequences of the Bcl2 gene. The nanocarriers were synthesized by loading Myc ODNs and selenium into chitosan (Chi-Se-DEC), which was then encapsulated in niosome-nanocarriers (NISM@Chi-Se-DEC). FT-IR, DLS, FESEM, and hemolysis tests were applied to confirm its characterization and physicochemical properties. Moreover, cellular uptake, cellular toxicity, apoptosis, cell cycle, and scratch repair assays were performed to evaluate its anticancer effects on cancer cells. All anticancer assessments were repeated under X-ray irradiation conditions (fractionated 2Gy). Physicochemical characteristics of niosomes containing SeNPs and ODNs showed that it is synthesized appropriately. It revealed that the anticancer effect of NISM@Chi-Se-DEC can be significantly improved in combination with X-ray irradiation treatment. It can be concluded that NISM@Chi-Se-DEC nanocarriers have the potential as a therapeutic agent for cancer treatment, particularly in combination with radiation therapy and in-vivo experiments are necessary to confirm the efficacy of this nano-drug.

Targeted anti-tumor synergistic effects of Myc decoy oligodeoxynucleotides-loaded selenium nanostructure combined with chemoradiotherapy on LNCaP prostate cancer cells.

In the present study, we investigated the synergistic effects of targeted methotrexate-selenium nanostructure containing Myc decoy oligodeoxynucleotides along with X-irradiation exposure as a combination therapy on LNCaP prostate cancer cells. Myc decoy ODNs were designed based on the promoter of Bcl-2 gene and analyzed by molecular docking and molecular dynamics assays. ODNs were loaded on the synthesized Se@BSA@Chi-MTX nanostructure. The physicochemical characteristics of nanostructures were determined by FTIR, DLS, UV-vis, TEM, EDX, in vitro release, and hemolysis tests. Subsequently, the cytotoxicity properties of them with and without X-irradiation were investigated by uptake, MTT, cell cycle, apoptosis, and scratch assays on the LNCaP cell line. The results of DLS and TEM showed negative charge (-9 mV) and nanometer size (40 nm) for Se@BSA@Chi-DEC-MTX NPs, respectively. The results of FTIR, UV-vis, and EDX showed the proper interaction of different parts and the correct synthesis of nanoparticles. The results of hemolysis showed the hemocompatibility of this nanoparticle in concentrations less than 6 mg/mL. The ODNs release from the nanostructures showed a pH-dependent manner, and the release rate was 15% higher in acidic pH. The targeted Se@BSA@Chi-labeled ODN-MTX NPs were efficiently taken up by LNCaP cells by targeting the prostate-specific membrane antigen (PSMA). The significant synergistic effects of nanostructure (containing MTX drug) treatment along with X-irradiation showed cell growth inhibition, apoptosis induction (~57%), cell cycle arrest (G2/M phase), and migration inhibition (up to 90%) compared to the control. The results suggested that the Se@BSA@Chi-DEC-MTX NPs can potentially suppress the cell growth of LNCaP cells. This nanostructure system can be a promising approach for targeted drug delivery and chemoradiotherapy in prostate cancer treatment.

Biogenic and facile synthesis of selenium nanoparticles using Vaccinium arctostaphylos L. fruit extract and anticancer activity against in vitro model of breast cancer.

Biogenic synthesis of selenium nanoparticles (SeNPs) using plant extracts has emerged as a promising alternative approach to traditional chemical synthesis. The current study aims to introduce a safe, low-cost, and green synthesis of SeNPs using fresh fruit extract of Vaccinium arctostaphylos L. The biogenic synthesis of SeNPs was confirmed by different analyses including ultraviolet-visible spectrophotometry, Fourier transform infrared, and energy-dispersive X-ray. Also, the crystalline nature, size, and morphology of the obtained SeNPs were characterized by X-ray diffraction, dynamic light scattering, field emission scanning electron microscopy, and transmission electron microscopy techniques. The SeNPs were successfully synthesized with fruit extract of V. arctostaphylos L. in a regular spherical form and narrow size distribution with suitable zeta-potential values and exhibited appropriate biocompatibility. It revealed that the synthesized SeNPs can significantly inhibit the growth of 4T1 breast cancer cells with an IC50 of ∼84.19 ± 25.96 µg/ml after 72 h treatment. Overall, it can be concluded that the green synthesized SeNPs can be attractive, nontoxic, and eco-friendly candidates for drug delivery or medicinal applications.

Hybrid of niosomes and bio-synthesized selenium nanoparticles as a novel approach in drug delivery for cancer treatment.

The current study intends to investigate a novel drug delivery system (DDS) based on niosomes structure (NISM) and bovine serum albumin (BSA) which was formulated to BSA coated NISM (NISM-B). Also, selenium nanoparticles (SeNPs) have been prepared by BSA mediated biosynthesis. Finally, the NISM-B was hybridized with SeNPs and was formulated as NISM-B@SeNPs for drug delivery applications. Physicochemical properties of all samples were characterized by UV-Vis spectroscopy, FT-IR, DLS, FESEM, and EDX techniques. The cytotoxicity of all samples against A549 cell line was assessed by cell viability analysis and flow cytometry for apoptotic cells as well as RT-PCR for the expression of MDR-1, Bax, and Bcl-2 genes. Besides, in vivo biocompatibility was performed by LD50 assay to evaluate the acute toxicity. The proposed formulation has a regular spherical shape and approximately narrow size distribution with proper zeta-potential values; the proposed DDS revealed a good biocompatibility. The compound showed a significant cytotoxic effect against A549 cell line. Although the Bax/Bcl-2 expression ratio was significantly in NISM-B@SeNPs- treated cancer cells, the expression of MDR-1 was non-significantly lower in NISM-B@SeNPs-treated cancer cells. The obtained results suggest that the proposed DDS presents a promising approach for drug delivery, co-delivery and multifunctional biomedicine applications.

Selegiline (L-Deprenyl) Mitigated Oxidative Stress, Cognitive Abnormalities, and Histopathological Change in Rats: Alternative Therapy in Transient Global Ischemia.

Selegiline (L-deprenyl) is the major drug which is used in the treatment of Parkinson's disease because of its neurotrophic and antiapoptotic properties. Previous studies suggested that low dose of L-methamphetamine (L-METH) caused lower mortality rate in patients with severe traumatic brain injury. As L-methamphetamine is one of the metabolites of selegiline, the present study aims to examine whether L-deprenyl can improve cognitive, biochemical, and histopathological injury in animal model of transient global ischemia. The animals were randomized in ten groups orally gavaged three times a week for 28 days. Then, novel object recognition (NOR) was conducted to assess their behavioral abnormality. After scarification of the rats, their brains were divided into two sections to measure oxidative stress parameters and perform pathological evaluations in rats. Our data revealed the involvement of oxidative stress, behavioral despair, and pathological data in transient global ischemia rats. Significant recovery in cognitive behavior, oxidative stress biomarker, and number of dead cell in histopathological assay was observed in rats treated with 1,2 and 4 mg/kg of selegiline. So, selegiline appears to be useful in alternative therapy of transient global ischemia.