A Dual Bioconjugated Virus-Like Nanoparticle as a Drug Delivery System and Comparison with a pH-Responsive Delivery System

Modifications of virus-like nanoparticles (VLNPs) using chemical conjugation techniques have brought the field of virology closer to nanotechnology. The huge surface area to volume ratio of VLNPs permits multiple copies of a targeting ligand and drugs to be attached per nanoparticle. By exploring the chemistry of truncated hepatitis B core antigen (tHBcAg) VLNPs, doxorubicin (DOX) was coupled covalently to the external surface of these nanoparticles via carboxylate groups. About 1600 DOX molecules were conjugated on each tHBcAg VLNP. Then, folic acid (FA) was conjugated to lysine residues of tHBcAg VLNPs to target the nanoparticles to cancer cells over-expressing folic acid receptor (FR). The result demonstrated that the dual bioconjugated tHBcAg VLNPs increased the accumulation and uptake of DOX in the human cervical and colorectal cancer cell lines compared with free DOX, resulting in enhanced cytotoxicity of DOX towards these cells. The fabrication of these dual bioconjugated nanoparticles is simple, and drugs can be easily conjugated with a high coupling efficacy to the VLNPs without any limitation with respect to the cargo's size or charge, as compared with the pH-responsive system based on tHBcAg VLNPs. These dual bioconjugated nanoparticles also have the potential to be modified for other combinatorial drug deliveries.