Hepatitis B virus envelope L proteins produced in yeast cells form hollow nanoparticles (L particles, average diameter 220 nm) displaying human liver-specific receptor. Recently, the L particles were found to incorporate genes, proteins, and drugs, and act as an efficient pinpoint delivery system to human liver-derived tissues in xenograft models. By substituting the epidermal growth factor (EGF) for human liver-specific receptor, the mutated L particles showed the affinity to the EGF receptor, not to human liver. Other similar HBV envelope proteins, e.g., M and S particles, have already been commercialized for hepatitis B vaccine, strongly suggesting the safety of L particles in human. These results indicate that the hollow bio-nanoparticles are a promising candidate for the next-generation platform of DDS, especially that related to gene therapy.