Expression of squamous cell carcinoma antigen‐1 in liver enhances the uptake of hepatitis B virus envelope‐derived bio‐nanocapsules in transgenic rats

Kasuya, Tadashi; Nomura, Shosaku; Matsuzaki, Takashi; Jung, Joohee; Yamada, Tesshi; Tatematsu, Kenji; Okajima, Toshihide; Tanizawa, Katsuyuki; Kuroda, Shinya

doi:10.1111/j.1742-4658.2008.06698.x

Cited by 11 publications

(5 citation statements)

References 30 publications

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“…HSPG is abundantly expressed in the extracellular matrix of various tissues, which could interact with AGL of S region[ 8 , 11 ]. The binding of BNC to human hepatic cells[ 32 ] was efficiently suppressed by heparin[ 38 ]. Since the membrane topology of BNC is similar with HBV, HSPG might act as a low-affinity receptor for BNC.…”

Section: Bnc As a Model Of Hbvmentioning

confidence: 99%

Elucidation of the early infection machinery of hepatitis B virus by using bio-nanocapsule

Liu¹,

Somiya²,

Kuroda³

2016

WJG

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Currently, hepatitis B virus (HBV), upon attaching to human hepatocytes, is considered to interact first with heparan sulfate proteoglycan (HSPG) via an antigenic loop of HBV envelope S protein. Then, it is promptly transferred to the sodium taurocholate cotransporting polypeptide (NTCP) via the myristoylated N-terminal sequence of pre-S1 region (from Gly-2 to Gly-48, HBV genotype D), and it finally enters the cell by endocytosis. However, it is not clear how HSPG passes HBV to NTCP and how NTCP contributes to the cellular entry of HBV. Owing to the poor availability and the difficulty of manipulations, including fluorophore encapsulation, it has been nearly impossible to perform biochemical and cytochemical analyses using a substantial amount of HBV. A bio-nanocapsule (BNC), which is a hollow nanoparticle consisting of HBV envelope L protein, was efficiently synthesized in Saccharomyces cerevisiae. Since BNC could encapsulate payloads (drugs, genes, proteins) and specifically enter human hepatic cells utilizing HBV-derived infection machinery, it could be used as a model of HBV infection to elucidate the early infection machinery. Recently, it was demonstrated that the N-terminal sequence of pre-S1 region (from Asn-9 to Gly-24) possesses low pH-dependent fusogenic activity, which might play a crucial role in the endosomal escape of BNC payloads and in the uncoating process of HBV. In this minireview, we describe a model in which each domain of the HBV L protein contributes to attachment onto human hepatic cells through HSPG, initiation of endocytosis, interaction with NTCP in endosomes, and consequent provocation of membrane fusion followed by endosomal escape.

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Section: Bnc As a Model Of Hbvmentioning

confidence: 99%

Elucidation of the early infection machinery of hepatitis B virus by using bio-nanocapsule

Liu¹,

Somiya²,

Kuroda³

2016

WJG

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“…Experiments performed with the CysPreS1 peptide did not reveal any interaction (see the Supporting Information). Such an outcome was likely the result of the low molecular weight of the peptide, which reduced the amplitude of the instrument response, and of the possible low affinity of the peptide for SB3 at the concentration interval explored. , However, 1 -AuNPs revealed a quite-strong binding (Figure ). Association and dissociation profiles were rather complex and could be fitted only with a kinetic model, which includes two different binding modes of the nanoparticles to SB3 (see the Supporting Information).…”

Section: Resultsmentioning

confidence: 99%

“…This protein is frequently up-regulated in several malignancies of epithelial origin and of the liver. Indeed, it is undetectable in normal hepatocytes, but it is overexpressed in hepatocellular carcinoma (HCC) and in hepatoblastoma. − A few years ago, some researchers − have demonstrated that SB3 is also a target of the hepatitis B virus (HBV), and a key recognition element is the PreS1(21–47) peptide, which is a fragment of one of the proteins composing the viral envelope. Other target proteins have been suggested for the HBV capsid, particularly for the PreS1 region.…”

Section: Introductionmentioning

confidence: 99%

Binding and Uptake into Human Hepatocellular Carcinoma Cells of Peptide-Functionalized Gold Nanoparticles

et al. 2016

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One of the most daunting challenges of nanomedicine is the finding of appropriate targeting agents to deliver suitable payloads precisely to cells affected by malignancies. Even more complex is the ability to ensure that the nanosystems enter those cells. Here, we use 2 nm (metal core) gold nanoparticles to target human hepatocellular carcinoma (HepG2) cells stably transfected with the SERPINB3 (SB3) protein. The nanoparticles were coated with a 85:15 mixture of thiols featuring, respectively, a phosphoryl choline (to ensure water solubility and biocompatibility) and a 28-mer peptide corresponding to the amino acid sequence 21–47 of the hepatitis B virus-PreS1 protein (PreS1(21–47)). Conjugation of the peptide was performed via the maleimide–thiol reaction in methanol, allowing the use of a limited amount of the targeting molecule. This is an efficient procedure also in the perspective of selecting libraries of new targeting agents. The rationale behind the selection of the peptide is that SB3, which is undetectable in normal hepatocytes, is overexpressed in hepatocellular carcinoma and in hepatoblastoma and has been proposed as a target of the hepatitis B virus (HBV). For the latter, the key recognition element is the PreS1(21–47) peptide, which is a fragment of one of the proteins composing the viral envelope. The ability of the conjugated nanoparticles to bind the target protein SB3, expressed in liver cancer cells, was investigated by surface plasmon resonance analysis and in vitro via cellular uptake analysis followed by atomic absorption analysis of digested samples. The results showed that the PreS1(21–47) peptide is a suitable targeting agent for cells overexpressing the SB3 protein. Even more important is the evidence that the gold nanoparticles are internalized by the cells. The comparison between the surface plasmon resonance analysis and the cellular uptake studies suggests that the presentation of the protein on the cell surface is critical for efficient recognition.

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“…The addition of lipids to bionanocapsules produced a bionanocapsule-liposomal complex, which had greater stability when compared with HBV bionanocapsules [169]. Liposome-bionanocapsule complexes are produced at sizes less than 200 nm, preventing the removal of the formulation by macrophages in the bloodstream [163,170].…”

Section: Bionanocapsule-liposome Complexesmentioning

confidence: 99%

Properties, Engineering and Applications of Lipid-Based Nanoparticle Drug-Delivery Systems: Current Research and Advances

Buse

El‐Aneed²

2010

Nanomedicine

103

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Lipid-based drug-delivery systems have evolved from micro- to nano-scale, enhancing the efficacy and therapeutic applications of these delivery systems. Production of lipid-based pharmaceutical nanoparticles is categorized into top-down (fragmentation of particulate material to reduce its average total dimensions) and bottom-up (amalgamation of molecules through chemical interactions creating particles of greater size) production methods. Selection of the appropriate method depends on the physiochemical properties of individual entities within the nanoparticles. The production method also influences the type of nanoparticle formulations being produced. Liposomal formulations and solid-core micelles are the most widely utilized lipid-based nanoparticles, with surface modifications improving their therapeutic outcomes through the production of long-circulating, tissue-targeted and/or pH-sensitive nanoparticles. More recently, solid lipid nanoparticles have been engineered to reduce toxicity toward mammalian cells, while multifunctional lipid-based nanoparticles (i.e., hybrid lipid nanoparticles) have been formulated to simultaneously perform therapeutic and diagnostic functions. This article will discuss novel lipid-based drug-delivery systems, outlining the properties and applications of lipid-based nanoparticles alongside their methods of production. In addition, a comparison between generations of the lipid-based nano-formulations is examined, providing insight into the current directions of lipid-based nanoparticle drug-delivery systems.

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Expression of squamous cell carcinoma antigen‐1 in liver enhances the uptake of hepatitis B virus envelope‐derived bio‐nanocapsules in transgenic rats

Cited by 11 publications

References 30 publications

Elucidation of the early infection machinery of hepatitis B virus by using bio-nanocapsule

Elucidation of the early infection machinery of hepatitis B virus by using bio-nanocapsule

Binding and Uptake into Human Hepatocellular Carcinoma Cells of Peptide-Functionalized Gold Nanoparticles

Properties, Engineering and Applications of Lipid-Based Nanoparticle Drug-Delivery Systems: Current Research and Advances

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