Prediction of Protein Targets in Ovarian Cancer Using a Ru-Complex and Carbon Dot Drug Delivery Therapeutic Nanosystems: A Bioinformatics and µ-FTIR Spectroscopy Approach.

We predicted the protein therapeutic targets specific to a Ru-based potential drug and its combination with pristine and N-doped carbon dot drug delivery systems, denoted as RuCN/CDs and RuCN/N-CDs. Synchrotron-based FTIR microspectroscopy (µFTIR) in addition to bioinformatics data on drug structures and protein sequences were applied to assess changes in the protein secondary structure of A2780 cancer cells. µFTIR revealed the moieties of the target proteins' secondary structure changes only after the treatment with RuCN and RuCN/N-CDs. A higher content of α-helices and a lower content of β-sheets appeared in A2780 cells after RuCN treatment. Treatment with RuCN/N-CDs caused a substantial increase in parallel β-sheet numbers, random coil content, and tyrosine residue numbers. The results obtained suggest that the mitochondrion-related proteins NDUFA1 and NDUFB5 are affected by RuCN either via overexpression or stabilisation of helical structures. RuCN/N-CDs either induce overexpression of the β-sheet-rich protein NDUFS1 and affect its random coil structure or interact and stabilise its structure via hydrogen bonding between -NH2 groups from N-CDs with protein C=O groups and -OH groups of serine, threonine, and tyrosine residues. The N-CD nanocarrier tunes this drug's action by directing it toward a specific protein target, changing this drug's coordination ability and inducing changes in the protein's secondary structures and function.