Viral Protein Coat-Based Nanoparticle Delivery System Targets Breast Cancer Cells

A novel transport system for targeted delivery of toxic chemotherapeutic agents or labile protein-based vaccines was based on nanoparticles fashioned from empty hepatitis E virus capsids.

Since hepatitis E is transmitted through the digestive system and viral RNA is present in the stools of patients with the disease, investigators at the University of California, Davis (USA) speculated that the viral protein coat would protect whatever compounds were trapped within.

The investigators treated empty hepatitis E virus particles so that five surface-exposed residues were mutated to cysteine to allow conjugation to maleimide-linked chemical groups via thiol-selective linkages. The engineered virus-like nanoparticles were then covalently conjugated to a breast cancer recognized ligand, LXY30 and an amine-coupled near-infrared fluorescence dye.

The viral nanoparticles were evaluated for ability to bind and enter a breast cancer cell line and for tumor targeting in vivo to breast cancer tissue in mice. Results published in the February 1, 2016, issue of the journal Nanomedicine revealed that the engineered virus-like nanoparticle not only targeted cancer cells, but also failed to interact with native hepatitis E virus antibodies due to epitope disruption at the antibody-binding site.

This study demonstrated that chemical conjugation with target ligand was capable of eliciting uptake of nanoparticles specifically into breast cancer cells. In vivo and ex vivo imaging confirmed the specific uptake of these nanoparticles by mouse breast tumors. A novel feature of these viral-based nanoparticles is that they were able to conjugate synthetic macromolecules and non-proteinogenic amino acids without compromising particle integrity. In addition, the preserved interior surface of the nanocapsid enabled the encapsulation of negatively charged payloads such as microRNA.

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University of California, Davis