Aim: To compare the pharmacokinetics and efficacy of doxorubicin containing plant virus nanoparticles (PVNs) with PEGylated liposomal doxorubicin (PLD) and small molecule doxorubicin in two mouse models of cancer. Materials & methods: Studies were performed in A375 melanoma and intraperitoneal SKOV3ip1 ovarian cancer xenografts. The PVNs were administered in lower and more frequent doses in the ovarian model. Results: The PVNs were more efficacious than PLD and small molecule doxorubicin in the ovarian cancer model, but not in the melanoma cancer model. The pharmacokinetics profiles of the PVNs showed fast plasma clearance, but more efficient tumor delivery as compared with other carrier-mediated agents. Conclusion: PVNs administered at lower repeated doses provide both pharmacologic and efficacy advantages compared with PLD.