471855 Engineering of Virus-like Particles for Targeted Delivery of Cancer Drugs

Monday, November 14, 2016
Grand Ballroom B (Hilton San Francisco Union Square)
Maya Nagasawa1, Marcus Rohovie2 and James Swartz1,2, (1)Bioengineering, Stanford University, Stanford, CA, (2)Chemical Engineering, Stanford University, Stanford, CA

Prostate cancer is the second leading cause of cancer death in American men, and chemotherapy has been limited because of harsh side effects caused by the systemic delivery of cancer drugs including docetaxel. Virus-like particles (VLPs) designed for targeted drug delivery to prostate cancer cells can help increase the docetaxel efficacy and reduce side effects. VLPs are hollow and non-infectious nanoparticles derived from the viral capsid, and they have been engineered to be used as targeted drug delivery vehicles by loading therapeutic cargo inside the capsid. The Swartz lab has engineered Hepatitis B core VLPs to be stable during manufacture and storage, but to lose stability under cytoplasmic conditions. This allows the drug cargo to be released inside the cells. Targeting molecules, such as antibody fragments that bind to the cell surface markers of prostate cancer, can be used to direct the VLPs to prostate cancer cells to reduce the undesired side effects. The Swartz lab has developed a process to functionalize the VLP surface with these ligands using non-natural amino acid incorporation and cell-free protein synthesis. This work focuses on recent efforts for the effective loading and retention of docetaxel inside the VLP. For effective loading, we introduced several different C-termini that extend into the VLP interior, on which different types of charged and hydrophobic cancer drugs will adsorb by electrostatic and hydrophobic interactions. We further engineered the VLPs to constrict the pores for the better retention of the cargo during the circulation. The final delivery vehicle functionalized with the targeting molecules will provide improved efficacy and reduced side effects compared to the systemic administration of docetaxel.

Extended Abstract: File Not Uploaded