Tobacco mosaic virus delivery of mitoxantrone for cancer therapy

Abstract

Mitoxantrone (MTO) is a topoisomerase II inhibitor which has been used to treat various forms of cancer either as a solo chemotherapy regimen or as a component in cocktail treatments. However, as with other anti-neoplastic agents, MTO has severe cardiac side effects. Therefore, a drug delivery approach holds promise to improve the safety and applicability of this chemotherapy. Here, we report the application of a plant virus-based nanotechnology derived from tobacco mosaic virus (TMV) as a delivery vehicle for MTO towards cancer therapy. TMV is a high aspect-ratio, soft-matter nanotube with dimensions of 300 × 18 nm and a 4 nm wide channel. The surface chemistry of the interior and exterior TMV surfaces is distinct and we established charge-driven drug loading strategies to encapsulate therapeutics for drug delivery. We demonstrate effective MTO loading into TMV yielding ∼1000 MTO per TMV carrier. The treatment efficacy of MTO-loaded TMV (_MTOTMV) was assessed in in vitro and in vivo models. In vitro testing confirmed that MTO maintained its efficacy when delivered by TMV in a panel of cancer cell lines. Drug delivery in vivo using a mouse model of triple negative breast cancer demonstrated the superior efficacy of TMV-delivered MTO vs. free MTO. This study demonstrates the potential of plant virus-based nanotechnology for cancer therapy and drug delivery.