Zoe Merz Rose Hills
Site-Specific Modification of Virus-Like Particles for Cancer Drug Delivery
Common cancer therapies, such as chemotherapy, have harsh side effects because they damage both healthy and cancerous cells. Therapies that deliver drugs directly to cancer cells eliminate this issue. Protein nanocages, coupled with cancer targeting ligands, are attractive drug delivery vessels due to their biocompatibility and reduced toxicity. One such protein nanocage is the MS2 bacteriophage Virus Like Particle (VLP) coat protein. This 27 nm diameter protein shell has shown promise for delivery applications due to its thermostability and high modifiability. To be used as a drug delivery system, MS2 must be loaded with a cancer therapy and modified on the exterior with a cancer cell targeting ligand. One promising cancer therapy is Cyclic Dinucleotides (CDNs). When delivered to a cell, CDNs activate the STING pathway, which signals the immune system to destroy that cell. In my project, I will be modifying the MS2 coat protein with CDNs on the interior and cancer cell targeting ligands on the exterior. I will then assess its viability in drug delivery through cell binding studies.