Tumor targeting using canine parvovirus nanoparticles

Abstract

Advances in genetics, proteomics and cellular and molecular biology are being integrated and translated to develop effective methods for the prevention and control of cancer. One such combined effort is to create multifunctional nanodevices that will specifically recognize tumors and thus enable early diagnosis and provide targeted treatment of this disease. Viral particles are being considered for this purpose since they are inherently nanostructures with well-defined geometry and uniformity, ideal for displaying molecules in a precise spatial distribution at the nanoscale level and subject to greater structural control. Viruses are presumably the most efficient nanocontainer for cellular delivery as they have naturally evolved mechanisms for binding to and entering cells. Virus-based systems typically require genetic or chemical modification of their surfaces to achieve tumor-specific interactions. Interestingly, canine parvovirus (CPV) has a natural affinity for transferrin receptors (TfRs) (both of canine and human origin) and this property could be harnessed as TfRs are over-expressed by a variety of human tumor cells. Since TfR recognition relies on the CPV capsid protein, we envisioned the use of virus or its shells as tumor targeting agents. We observed that derivatization of CPV virus-like particles (VLPs) with dye molecules did not impair particle binding to TfRs or internalization into human tumor cells. Thus CPV-based VLPs with a natural tropism for TfRs hold great promise in the development of novel nanomaterial for delivery of a therapeutic and/or genetic cargo. © 2009 Springer.