Virus-Like Particle-Encapsulated Doxorubicin Enters and Kills Murine Tumor Cells Different From Free Doxorubicin.

The use of nanoparticles as chemotherapeutic carriers has been suggested as a way to overcome a range of side effects associated with classical cancer treatment such as poor selectivity and tumor resurgence. Obtaining precise control of size and shape of therapeutic nanoparticles is crucial to optimize targeting of tumor sites. In this work we show that a previously developed system of polypeptide encapsulating individual DNA molecules, that forms rod-shaped nanoparticles of precisely controlled aspect ratio, can be loaded with the DNA-intercalating chemotherapeutic drug doxorubicin (DOX). We characterize size and shape of the DOX loaded Virus-Like DNA Particles (DOX-VLDP) and show that in this system the DOX payload does not leak out. Through in vitro cell studies we show that DOX-VLDP are internalized by melanoma tumor cells (B16F10 cells) in a delayed and endocytosis-dependent way culminating in increased cytotoxicity and selectivity to tumor cells in comparison with free DOX. In addition, we find that DOX-VLDP trigger apoptosis and autophagy pathways in treated cells. Taken together our data on the DOX-VLDP nanoparticles shows that they kill cancer cells differently from free DOX. This article is protected by copyright. All rights reserved.