Targeted Virus Nanoparticles for Localized Chemotherapy of Breast Cancer

A critical difficulty in designing nanotherapeutics is in developing highly targeted platforms that can reach target sites with high efficiency. Additionally, due to the high degree of heterogeneity in breast tumors within a patient as well as between patients, there is currently no one biomarker available that specifically identifies all breast cancer cells. To overcome these obstacles, we have developed a novel drug delivery system based on adeno-associated virus (AAV) to deliver chemotherapeutic agents specifically to breast cells and limit the exposure of drugs to normal non-breast tissues. AAV is a 25 nm virus that is currently in clinical trials for a variety of gene therapy applications. The AAV capsid is a supramolecular assembly of 60 protein subunits, lending itself well to multivalent conjugation of drug molecules. We have used directed evolution to create virus nanoparticles that can specifically bind breast tissue. Paclitaxel, chemically modified with N-hydroxysuccinimide, was covalently attached to the virus capsid surface. Drug-virus nanoparticles were assayed for degree of conjugation with UV-vis and MALDI-MS, proper capsid assembly with ELISA and TEM, genomic packaging with Q-PCR, and cytotoxicity with cell viability assays. This work will offer superior targeting of breast tissues and provide greater drug payload. It has the potential of significantly decreasing the morbidity associated with systemic chemotherapy.