Details

Autor(en) / Beteiligte

• Sakai, Chiho
• Hosokawa, Kohei
• Watanabe, Tadashi
• Suzuki, Youichi
• Nakano, Takashi
• Ueda, Keiji
• Fujimuro, Masahiro

Titel

Human hepatitis B virus-derived virus-like particle as a drug and DNA delivery carrier

Ist Teil von

• Biochemical and biophysical research communications, 2021-12, Vol.581, p.103-109

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2021

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• The controlled release of medications using nanoparticle-based drug delivery carriers is a promising method to increase the efficacy of pharmacotherapy and gene therapy. One critical issue that needs to be overcome with these drug delivery carriers is their target specificity. We focused on the cell tropism of a virus to solve this issue, i.e., we attempted to apply hepatitis B virus-like particle (HBV-VLP) as a novel hepatic cell-selective carrier for medication and DNA. To prepare HBV-VLP, 293T cells were transfected with expression plasmids carrying HBV envelope surface proteins, large envelope protein (L), and small envelope protein (S). After 72 h post-transfection, VLP-containing culture supernatants were harvested, and HBV-VLP was labeled with red fluorescent dye (DiI) and was purified by sucrose gradient ultracentrifugation. An anticancer drugs (geldanamycin or doxorubicin) and GFP-expressing plasmid DNA were incorporated into HBV-VLP, and medication- and plasmid DNA-loaded VLPs were prepared. We evaluated their delivery capabilities into hepatocytes, other organ-derived cells, and hepatocytes expressing sodium taurocholate cotransporting polypeptide (NTCP), which functions as the cellular receptor for HBV by binding to HBV L protein. HBV-VLP selectively delivered both anticancer drugs and plasmid DNA not into HepG2, Huh7, and other organ cells but into HepG2 cells expressing NTCP. In summary, we developed a novel delivery nanocarrier using HBV-VLP that could be used as a hepatitis selective drug- and DNA-carrier for cancer treatment and gene therapy. •HBV infects with hepatic cells via spike L protein that binds to the hepatic NTCP.•We focused on the cell tropism of HBV to improve hepatocyte specificity of DDS.•We prepared HBV-like nanoparticle (VLP) having HBV spike L and envelope S proteins.•VLP selectively delivered anticancer drugs and GFP-plasmid to NTCP-positive cells.•Our VLP could be useful as a hepatitis-selective drug and DNA delivery carrier.