Final Report Summary - BTVI (First Biodegradable Biocatalytic VascularTherapeutic Implants)
These days, medicinal chemists synthesize drugs that can counter the cause of virtually any disease - but this is not to say that doctors can cure the patients from these diseases. Administered as is, drugs do not know where they need to be, do not get to their site of action in sufficient concentration, and their side effects often negate the therapeutic benefits. As an effective solution, this team established the means to perform localized synthesis of drugs, precisely at the site where the drug is needed. To achieve this, we use “prodrugs” – cunning molecules that have no activity but reveal the incorporated therapeutic upon bioconversion. We established this bioconversion using natural enzymes, specifically such as to locally synthesize anticancer drugs, vasodilation medicine, and antibacterial therapeutics to prevent bacterial colonization of implants. We also discovered that drug synthesis occurs on the surface of metallic implants that are already in medical use; we designed innovative prodrugs that reach the implant surface and thereupon release antibacterial drugs. We also developed prodrugs that accumulate within tumors and specifically release the incorporated toxin in the tumor microenvironment, thus comprising a safe, effective measure to suppress cancer cell growth. Taken together, this project developed “enzyme prodrug therapy” into a well performing biomedical platform.