Abstract
(1) Background: As nanoparticles containing the hepatitis B virus (HBV) large (L) surface protein produced in yeast are expected to be useful as a carrier for targeting hepatocytes, they are also referred to as bio-nanocapsules (BNCs). However, a definitive cell membrane receptor for BNC binding has not yet been identified. (2) Methods: By utilizing fluorescence-labeled BNCs, we examined BNC binding to the scavenger receptor class B type 1 (SR-B1) expressed in HEK293T cells. (3) Results: Analyses employing SR-B1 siRNA and expression of SR-B1 fused with a green fluorescent protein (SR-B1-GFP) indicated that BNCs bind to SR-B1. As mutagenesis induced in the SR-B1 extracellular domain abrogates or attenuates BNC binding and endocytosis via SR-B1 in HEK293T cells, it was suggested that the ligand-binding site of SR-B1 is similar or close among high-density lipoprotein (HDL), silica, liposomes, and BNCs. On the other hand, L protein was suggested to attenuate an interaction between phospholipids and SR-B1. (4) Conclusions: SR-B1 can function as a receptor for binding and endocytosis of BNCs in HEK293T cells. Being expressed various types of cells, it is suggested that functions as a receptor for BNCs not only in HEK293T cells but also in other types of cells.
Highlights
In the hepatitis B virus (HBV) genome, three genes overlapped in a single open reading frame (ORF)encode surface proteins (HBs): large (L protein: pre-S1 + pre-S2 + S regions), middle (M protein: pre-S2 + S regions), and small (S protein: S region) [1]
We demonstrated that BNCs bind to HEK293T cells via scavenger receptor class B type 1 (SR-B1), based on the results of experiments using SR-B1 siRNA and the expression of SR-B1-GFP
We have previously revealed that liposomes comprising various phospholipids including PC, PE, and phosphatidic acid (PA) bind to SR-B1, and are endocytosed in HEK293T cells
Summary
In the HBV genome, three genes overlapped in a single open reading frame (ORF)encode surface proteins (HBs): large (L protein: pre-S1 + pre-S2 + S regions), middle (M protein: pre-S2 + S regions), and small (S protein: S region) [1]. Hollow phospholipid nanoparticles (PNPs) coated with L protein can be produced using yeast (Saccharomyces cerevisiae) introduced with a plasmid to express L protein. They have been expected to be useful as a carrier in drug delivery systems (DDS) to convey targeted bioactive substances to hepatocytes in vitro and in vivo. To use BNCs in vivo, escape mutant-type BNCs (emBNCs) have been developed to reduce the immunogenicity of L protein by the substitution of two amino acid residues (i.e., Q129R and G145R) in the S region. BNCs were once expected as a model mimicking HBsAg or HBV particles, the usefulness of BNCs as an HBV model is thought to be limited [6]
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