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Engineering virus-like particles for targeted delivery of anti-cancer drugs

Targeted anti-cancer drug delivery is important both to improve the drug efficacy at the tumor site and to reduce side effects. For this purpose, virus-like particles (VLPs) offer several potential advantages. VLPs are non-infectious and self-assembled nanoparticles derived from viral capsids. Compared to traditional antibody-drug conjugates, they have the potential to provide a better delivery system by encapsulating a high number of drugs, while protecting the drugs from the surrounding environment before reaching to the cancer cell. The Swartz Lab has been developing Hepatitis B core (HepBc) VLPs to have high stability during manufacture and storage, and to present a non-immunogenic surface that can be easily modified with multiple ligands. The HepBc VLPs were further engineered to load and retain > 300 anti-cancer drugs per particle. Taking advantage of the previous developments in bioconjugation, multiple ligands have been attached to the surface of the VLPs for immune system avoidance and specific targeting. First, displaying the CD47 extracellular domain, or endogenous "marker of self", avoids immune clearance by phagocytes. Second, displaying a DNA aptamer specific to prostate-specific membrane antigen (PSMA) allows the VLPs to specifically target PSMA+ prostate cancer cells, our model disease target. This triggers internalization of the VLPs into the cells where the VLPs will open to release their cytotoxic cargo. Compared to the systemic administration of anti-cancer drugs, this VLP-based delivery vehicle will greatly increase drug efficacy while reducing side effects. Taken together, this will dramatically increase the patient's survival as well as quality of life.