Cucumber mosaic virus as drug delivery vehicle for doxorubicin

Abstract

Taking advantage of the unique structure feature of cucumber mosaic virus (CMV), we have anchored folic acid (FA) as targeting moiety on the rigid CMV capsid and loaded significant amount of doxorubicin (Dox) into the interior cavity of CMV through the formation of Dox–RNA conjugate to provide a nanosized control delivery system for cancer therapy. The FA–CMV–Dox assemblies were characterized using transmission electron microscopy and size exclusion chromatography, which disclose that they have comparable size and morphology to the native CMV particles. The Dox-loaded viral particles exhibit sustained in vitro Dox release profile over 5 days at physiological pH but can be liberated from the conjugates with the presence of elevated level of RNase. The in vitro effects of folate receptor (FR)-targeted CMV–Dox nanoconjugates on cellular internalization and cell proliferation were evaluated by live-cell imaging, MTT and TUNEL assay, respectively, in mouse cardiomyocytes and FR over expression OVCAR-3 tumor cells. The in vivo efficacy was also investigated in the OVCAR-3 BALB/c nude mouse xenograft model through histological alterations and TUNEL assessment. The FA–CMV–Dox particles significantly decrease the accumulation of Dox in the nuclei of mouse myocardial cells and improve the uptake of Dox in the ovarian cancer, leading to less cardiotoxicity and enhanced antitumor effect. We believe that CMV offers a new way to fabricate nanosized drug delivery vehicles.