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Abstract Objective Exosomes, membrane-enveloped vesicles found in various cell types, including Wharton’s jelly mesenchymal stem cells, play a crucial role in intercellular communication and regulation. Their use as a cell-free nanotechnology and drug delivery system has attracted attention. Triple-negative breast cancer (TNBC) is a major global health problem and is characterized by a high mortality rate. This study investigates the potential of Wharton’s Jelly mesenchymal stem cell-derived exosomes (WJ-Exo) as carriers of S3I-201 and their effects on STAT3 expression in breast cancer cell lines, and evaluates whether these exosomes can enhance the anti-tumor effect of S3I-201. Methods The filtered WJ-Exos were analyzed by Transmission Electron Microscopy (TEM), Scanning electron microscopy (SEM), Dynamic Light Scattering (DLS), flow cytometry, and Western blotting. These exosomes were then used for loading with S3I-201, resulting in the nano-formulation WJ-Exo(S3I-201). The effect of WJ-Exo(S3I-201) on 4T1 cancer cells was investigated in vitro using MTT assay, flow cytometry, wound healing assay, Western blotting and Quantitative Real-Time Polymerase chain reaction (qPCR) analysis. Finally, the therapeutic efficacy of the nano-formulation was investigated in vivo using a tumor-bearing mouse model. Results In vitro experiments showed that co-incubation of 4T1 cells with the nano-formulation resulted in a significant reduction in p-STAT3 levels, induction of apoptosis, modulation of Bcl-2, Bax and caspase-3 protein and gene expression, and inhibition of migration. In vivo, treatment of tumor-bearing mice with WJ-Exo(S3I-201) showed a strong antitumor effect that exceeded the efficacy observed in the S3I-201 group. Conclusion Our results demonstrate that WJ-Exo is an effective carrier for targeting S3I-201 to tumor cells and enhances the therapeutic efficacy of S3I-201 in tumor-bearing mice.

Ganoderma lucidum (G. lucidum) is a medicinal mushroom that is known for its ability to produce compounds with physiological effects on human health. This research was undertaken to amplify the production of bioactive components of G. lucidum under optimal cultivation conditions, obtained in a submerged state and utilized in solid state fermentation, with the purpose of enhancing antimicrobial and anticancer activities. The results indicated that titanium dioxide (TiO2 NPs), magnesium oxide nanoparticles (MgO2 NPs), and B6, along with glucose syrup and CLS syrups, were the most effective for producing GA, while wheat starch and whey protein, along with MgO2 NPs and B6 vitamin, stimulated polysaccharide production using the One Factor at a Time (OFAT) method. After screening, the response surface method (RSM) statistically indicated that the media containing 42.11 g/L wheat starch with 22 g/L whey protein and 50 g/L glucose syrup with 30 g/L CSL were found to be the best conditions for polysaccharide (21.47% of dry weight biomass) and GA (20.35 mg/g dry weight biomass) production, respectively. The moss of the fruit body of G. lucidum produced under optimal GA conditions had the highest diversity in flavonoids and phenolic acids and significant antimicrobial activity against Esherichia coli (E. coli) and Bacillus subtilis (B. subtilis). In addition, the IC50 levels of shell and stem of G. lucidum were 465.3 and 485.7 μg/mL, respectively, while the moss did not reach 50% inhibition. In the end, the statistical approaches utilized in this research to elevate the levels of bioactive components in the fruiting body of G. lucidum produced a promising natural source of antimicrobial and anticancer agents.