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

Autor: Sakai C; Department of Cell Biology, Kyoto Pharmaceutical University, Kyoto, 607-8412, Japan., Hosokawa K; Department of Cell Biology, Kyoto Pharmaceutical University, Kyoto, 607-8412, Japan., Watanabe T; Department of Cell Biology, Kyoto Pharmaceutical University, Kyoto, 607-8412, Japan., Suzuki Y; Department of Microbiology and Infection Control, Faculty of Medicine, Osaka Medical and Pharmaceutical University, Osaka, 569-8686, Japan., Nakano T; Department of Microbiology and Infection Control, Faculty of Medicine, Osaka Medical and Pharmaceutical University, Osaka, 569-8686, Japan., Ueda K; Division of Virology, Osaka University Graduate School of Medicine, Osaka, 565-0871, Japan., Fujimuro M; Department of Cell Biology, Kyoto Pharmaceutical University, Kyoto, 607-8412, Japan. Electronic address: fuji2@mb.kyoto-phu.ac.jp.
Jazyk: angličtina
Zdroj: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2021 Dec 03; Vol. 581, pp. 103-109. Date of Electronic Publication: 2021 Oct 07.
DOI: 10.1016/j.bbrc.2021.10.009
Abstrakt: 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.
(Copyright © 2021 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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