RESUMEN
The discovery of effective therapeutic approaches with minimum side effects and their tendency to completely eradicate the disease is the main challenge in the history of cancer treatment. Fenugreek (FGK) seeds are a rich source of phytochemicals, especially Diosgenin (DGN), which shows outstanding anticancer activities. In the present study, chitosan-silver nanoparticles (ChAgNPs) containing Diosgenin (DGN-ChAgNPs) were synthesized and evaluated for their anticancer activity against breast cancer cell line (MCF-7). For the physical characterization, the hydrodynamic diameter and zeta potential of DGN-ChAgNPs were determined to be 160.4 ± 12 nm and +37.19 ± 5.02 mV, respectively. Transmission electron microscopy (TEM) showed that nanoparticles shape was mostly round with smooth edges. Moreover, DGN was efficiently entrapped in nanoformulation with good entrapment efficacy (EE) of ~88 ± 4 %. The in vitro anti-proliferative activity of DGN-ChAgNPs was performed by sulforhodamine B (SRB) assay with promising inhibitory concentration of 6.902 ± 2.79 µg/mL. DAPI staining, comet assay and flow cytometry were performed to validate the anticancer potential of DGN-ChAgNPs both qualitatively and quantitatively. The percentage of survival rate and tumor reduction weight was evaluated in vivo in different groups of mice. Cisplatin was used as a standard anticancer drug. The DGN-ChAgNPs (12.5 mg/kg) treated group revealed higher percentage of survival rate and tumor reduction weight as compared to pure DGN treated group. These findings suggest that DGN-ChAgNPs could be developed as potential treatment therapy for breast cancer.
Asunto(s)
Antineoplásicos , Quitosano , Diosgenina , Nanopartículas del Metal , Nanopartículas , Animales , Ratones , Quitosano/química , Plata , Diosgenina/farmacología , Diosgenina/química , Antineoplásicos/farmacología , Antineoplásicos/química , Nanopartículas/químicaRESUMEN
Introduction: Cancer contributes to a high mortality rate worldwide spanning its diversity from genetics to resistant therapeutic response. To date emerging strategies to combat and manage cancer are particularly focused on the development of targeted therapies as conventional treatments account for the destruction of normal cells as well. In this regard, medicinal plant-based therapies are quite promising in imposing minimal side effects; however, limitations like poor bioavailability and stability of bioactive phytochemicals are associated with them. In parallel, nanotechnology provides nominal solution to deliver particular therapeutic agent without compromising its stability. Methods: In this study, Solanum nigrum, an effective medicinal plant, loaded arabinoxylan cross-linked ß-cyclodextrin nanosponges (SN-AXCDNS) were designed to evaluate antitumor activity against breast cancer. Therefore, SN-AXCDNS were prepared by using cross-linker melt method and characterized by physicochemical and pharmacological parameters. Results: Hydrodynamic size, zeta potential and entrapment efficiency (EE%) were estimated as 226 ± 4 nm, -29.15 ± 5.71 mV and 93%, respectively. Surface morphology of nanocomposites showed spherical, smooth, and porous form. Antitumor pharmacological characterization showed that SN loaded nanosponge demonstrated higher cytotoxicity (22.67 ± 6.11 µg/mL), by inducing DNA damage as compared to void SN extract. Flow cytometry analysis reported that encapsulated extract promoted cell cycle arrest at sub-G1 (9.51%). Moreover, in vivo analysis demonstrates the reduction in tumor weight and 85% survival chances in nanosponge treated mice featuring its effectiveness. In addition, in silico analysis revealed that ß-cyclodextrin potentially inhibits MELK in breast cancer cell lines (B.E = -10.1 Kcal/mol). Conclusion: Therefore, findings of current study elucidated the therapeutic potential of ß-cyclodextrin based nanosponges to be an alternative approach regarding the delivery and solubilization of antitumor drugs.