Green synthesis and anticancer activity of titanium dioxide nanoparticles using the endophytic fungus Aspergillus sp.

Titanium dioxide nanoparticles (TiO₂ NPs) have attracted significant attention for their unique physicochemical features and various applications. This study demonstrated the biosynthesis of TiO₂ NPs using Aspergillus fungal extract that served as a green and eco-friendly reducing and stabilizing agent. The biosynthesized nanoparticles were analyzed using SEM and TEM to determine their morphology, size, and distribution, FTIR to determine functional groups, and Zeta potential to assess their surface charge and stability. An extensive review of the Protein Data Bank (PDB) and literature indicated that TiO₂ could target various cancer-relevant matrix metalloproteinases. In vitro screening indicated promising anticancer effects against the MCF7 breast cancer cell line. To investigate the possible mode of action of TiO₂ NPs as an anticancer agent, human matrix metalloproteinase-3 was highlighted as a protein inhibited by metallic ions like PtCl₂. Therefore, we investigated whether TiO₂ could similarly interact with the active site of MMP-3. We hypothesized that TiO2 could interact with the MMP-3 active site and replace PtCl₂ with modeled TiO₂ in its co-crystallized binding site. A 100 ns-long MDS, binding free energy (ΔGBinding) of PtCl₂ and TiO₂ within MMP-3 binding site indicated that TiO2's enhanced binding affinity and stability, as evidenced by a ΔGBinding of -7.23 kcal/mol and average RMSD of 0.89 Å, compared to PtCl₂’s lower affinity. In conclusion, endophytic fungi can be used efficiently in the biosynthesis of nanoparticles. Our study indicated TiO2 NPs have a potential anticancer effect, suggesting TiO₂ binds to MMP3, potentially offering comparable inhibitory effects on the enzyme's activity.