Abstract
BACKGROUND AND PURPOSE: Prostate cancer is one of the most common cancers in the world. Anti-prostate cancer drugs such as docetaxel, doxorubicin, and cabazitaxel have drawbacks resulting from their low solubility, non-targeted transfer, and many side effects. Prostate-specific membrane antigen (PSMA) receptor is expressed on the surface of prostate cancer cells. It was known that "WQPDTAHHWATL" and "GRFLTGGTGRLLRIS" peptides tended to bind this receptor. THEORETICAL APPROACH: "WQPDTAHHWATL" and "GRFLTGGTGRLLRIS" peptides were attached to the C and N tails of albumin protein, and an engineered albumin was designed. Then, engineered albumin and the extracellular domain of PSMA were separately simulated for 100 ns. Afterward, the interaction of engineered albumin with anti-prostate cancer drugs and the PSMA domain was investigated independently by molecular docking, molecular dynamics simulation, and molecular mechanics energies/Poisson-Boltzmann surface area binding free energy methods. FINDINGS/RESULTS: The binding affinity order of drugs to engineered albumin was docetaxel, doxorubicin, and cabazitaxel, respectively. Also, the residence time of docetaxel was longer than that of other drugs. The final picture of complexes showed that cabazitaxel and docetaxel bound to site IB, and doxorubicin bound to site IIA of the recombinant albumin. Additionally, the C-terminus and N-terminus of the engineered albumin could bind to the PSMA receptor. CONCLUSION AND IMPLICATIONS: It can be concluded that this engineered albumin is useful for targeted drug delivery in prostate cancer.