Phytosynthesis of silver nanoparticles using Artemisia marschalliana Sprengel aerial part extract and assessment of their antioxidant, anticancer, and antibacterial properties

Soheil Salehi,1 Seyed Ataollah Sadat Shandiz,2 Farinaz Ghanbar,3 Mohammad Raouf Darvish,4 Mehdi Shafiee Ardestani,5 Amir Mirzaie,2 Mohsen Jafari6 1Department of Phytochemistry and Essential Oils Technology, Faculty of Pharmaceutical Chemistry, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran (IAUPS), 2Young Researchers and Elite Club, East Tehran Branch, Islamic Azad University, Tehran, 3Department of Biology, Tehran North Branch, 4Department of Chemistry, Shahre-Rey Branch, Islamic Azad University, Tehran, 5Department of Radiopharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, 6Department of Biology, Faculty of Science, Shahid Chamran University of Ahvaz, Ahvaz, Iran Abstract: A rapid phytosynthesis of silver nanoparticles (AgNPs) using an extract from the aerial parts of Artemisia marschalliana Sprengel was investigated in this study. The synthesized AgNPs using A. marschalliana extract was analyzed by UV–visible spectroscopy, X-ray diffraction, and Fourier transform infrared spectroscopy and further characterized by transmission electron microscopy, scanning electron microscopy, zeta potential, and energy-dispersive spectroscopy. Characteristic absorption bands of AgNPs were found near 430 nm in the UV–vis spectrum. Energy-dispersive spectroscopy analysis of AgNPs in the energy range 2–4 keV confirmed the silver signal due to surface plasmon resonance. Scanning electron microscopy and transmission electron microscopy results revealed that the AgNPs were mostly spherical with an average size ranging from 5 nm to 50 nm. The zeta potential value of -31 mV confirmed the stability of the AgNPs. AgNPs produced using the aqueous A. marschalliana extract might serve as a potent in vitro antioxidant, as revealed by 2,2-diphenyl-1-picryl hydrazyl assay. The present study demonstrates the anticancer properties of phytosynthesized AgNPs against human gastric carcinoma AGS cells. AgNPs exerted a dose-dependent inhibitory effect on the viability of cells. Real-time polymerase chain reaction was used for the investigation of Bax and Bcl-2 gene expression in cancer and normal cell lines. Our findings show that the mRNA levels of pro-apoptotic Bax gene expression were significantly upregulated, while the expression of anti-apoptotic Bcl-2 was declined in cells treated with AgNPs compared to normal cells. In addition, flow cytometric analysis showed that the number of early and late apoptotic AGS cells was significantly enhanced following treatment with AgNPs as compared to untreated cells. In addition, the AgNPs showed strong antibacterial properties against tested pathogenic bacteria such as Staphylococcus aureus, Bacillus cereus, Acinetobacter baumannii, and Pseudomonas aeruginosa. Based on the obtained data, we suggest that phytosynthesized AgNPs are good alternatives in the treatment of diseases because of the presence of bioactive agents. Keywords: silver nanoparticles, Artemisia marschalliana Sprengel, anticancer, antibacteria

Novel chlorambucil-conjugated anionic linear-globular PEG-based second-generation dendrimer: in vitro/in vivo improved anticancer activity

Artin Assadi,1 Vahideh Sharifi Najafabadi,1 Seyed Ataollah Sadat Shandiz,2 Azadah Shayeq Boroujeni,1 Sepehr Ashrafi,1 Ali Zaman Vaziri,1 Seyedeh Masoumeh Ghoreishi,1 Mohammad Reza Aghasadeghi,3 Seyed Esmaeil Sadat Ebrahimi,4 Morteza Pirali-Hamedani,4 Mehdi Shafiee Ardestani1 1Department of Radiopharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, 2Young Researchers and Elite Club, East Tehran Branch, Islamic Azad University, 3Department of Hepatitis and AIDS, Pasteur Institute of Iran, 4Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran Abstract: Evaluating the efficacy of anticancer drugs is an evolving and research-oriented issue. The objective of this study was to reduce the insolubility of chlorambucil (CBL) in water and improve the anticancer activity of CBL in vitro and in vivo through the conjugation of CBL with anionic linear-globular dendrimer (second generation, G2). In the current study, the anticancer activity among three groups that include CBL, CBL–G2 dendrimer, and control was measured in vitro and in vivo. In vitro studies showed that G2 anionic linear-globular polyethylene-glycol-based dendrimer, which conjugated to the CBL exterior through an ester linkage, was able to significantly improve the treatment efficacy over clinical CBL alone with respect to proliferation assay, 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide; half maximal inhibitory concentration (IC50) was calculated to be 141 µg/mL for CBL alone and 27.7 µg/mL for CBL–G2 dendrimer; P<0.05. In addition, CBL–G2 dendrimer conjugate forestalled the growth of MCF-7 cancerous cells in addition to enhancing the number of apoptotic and necrotic cells as demonstrated by an annexin V-fluorescein isothiocyanate assay. CBL–G2 dendrimer conjugate was able to checkmate antiapoptotic Bcl-2 expression and Bcl-2/Bax ratio in a large scale compared with the control group and CBL alone (P<0.005). In vivo studies showed that tumor treatment by CBL–G2 dendrimer conjugate outstrips the efficacy of treatment compared with CBL alone. The evaluation was based on reduction in tumor volume and tumor growth inhibition of murine 4T1 mammary tumor cells. Tumor volume of 140%±8% was measured in the treatment with CBL–G2 dendrimer, whereas 152%±13.5% was calculated in the treatment with free CBL (P<0.05). However, there were no significant differences in histological assay among the three groups. In conclusion, tumor growth suppression potential of CBL–G2 dendrimer, which was assessed in both in vitro and in vivo experiments, has provided empirical evidence to buttress the fact that this compound could be considered for functional cancer treatment with low side effects. Keywords: anionic linear-globular dendrimer, G2, chlorambucil, CBL, in vitro cytotoxicity, in vivo efficac