A Peptoid-based targeted Drug delivery system for the treatment of Metastatic cancer

Development of a targeted drug delivery system is a critical step in the effort to improve cancer treatments. Such a system would greatly reduce the harmful side effects of chemotherapy by delivering toxic drugs directly to cancerous cells. Peptoids—synthetic compounds that can be easily produced from readily available amine monomers—have great potential for use in targeted drug delivery. This project aimed to develop peptoids that would bind to specific proteins expressed on the surface of cancer cells. These peptoids could be combined into a complex that would bind to the proteins with an even greater affinity than the individual compounds. The peptoid complexes would serve as a targeting system for chemotherapeutic drugs, delivering them directly to cancer cells, thereby preventing healthy tissues from being harmed. The specific membrane proteins that are being targeted are lectin-like oxidized low-density lipoprotein receptors (LOX-1) and receptors for advanced glycation end-products (RAGE). Both LOX-1 and RAGE are expressed in higher concentrations on cancerous cells than on non-cancerous ones. A combinatorial peptoid library was created using five side chains that have been identified as being suitable for this application. Each peptoid is six monomers long, resulting in a theoretical library diversity of 15,625 different compounds. A small sample of the library was screened to qualitatively identify peptoids with the highest binding affinity for LOX-1. To determine the sequences (chemical structures) of the peptoids that displayed high LOX-1, an automated peptide sequencer was utilized. Unfortunately, the time to work through the technicalities of the sequencing process exceeded the length of the project-to-date. However, progress was made and the sequences may be determined in the near future. Eventually the process will be repeated to determine RAGE-binding peptoids and the peptoids will be combined in a chemotherapy drug targeting system