Virus-like Nanoparticles Derived from Parvovirus B19 Efficiently Internalize in Human Heptatocytes: A Biocompatible Delivery System for Peptides and Proteins

• Published in: ACS applied nano materials Vol. 2; no. 10; pp. 6178 - 6186
• Main Authors: Cayetano-Cruz, Maribel, Valadez-García, Josefina, Méndez, Carmen, Bustos-Jaimes, Ismael
• Format: Journal Article
• Language: English
• Published: American Chemical Society 25.10.2019
• Subjects: cell targeting; in vitro self-assembly; Parvovirus B19; virus-like nanoparticles; SpyTag/SpyCatcher
• ISSN: 2574-0970; 2574-0970
• DOI: 10.1021/acsanm.9b01018

Virus-like nanoparticles (VLNPs) are an excellent alternative for the polyvalent display of peptides and proteins with a broad spectrum of enzymatic and other activities, which allow targeted delivery of bioactive molecules. Precise targeting is a limiting step in the application of selective therapies that otherwise can produce adverse side effects on off-target sites. In this research, we took advantage of the ability of the structural domain VP2 of parvovirus B19 to coassemble with chimeric forms of itself to produce VLNPs. Two chimeras of VP2, one with the targeting peptide PreS1 from the hepatitis B virus (HBV) and the other with the bioconjugating peptide SpyTag, were used to construct hybrid VLNPs displaying both peptides. The hybrid particles were decorated with a fluorescent protein fused to the orthogonal partner of SpyTag, the SpyCatcher domain. Characterization of the particles indicated that ∼33% of the SpyTag peptides were conjugated with the SpyCatcher domain, making the VLNPs fluorescent. Structural analysis by transmission electron microscopy and atomic force microscopy revealed nearly spherical structures with regular sizes between 30 and 40 nm, in agreement with the expected size for these particles. Decorated VLNPs were capable of internalizing into hepatoma HepG2 cells as shown by fluorescent confocal microscopy. The results confirm the presence of both heterologous peptides on the surface of the hybrid VLNPs and represent a fully biocompatible hepatocyte-targeted delivery system for peptides and proteins. Additional molecules may be added to either the surface or the internal core of the particles to develop multicomponent cooperative cell-targeted therapies.