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Hao Li, Kenji Tatematsu, Masaharu Somiya, Masumi Iijima, Shun' Ichi Kuroda
Macrophage hyperfunction or dysfunction is tightly associated with various diseases, such as osteoporosis, inflammatory disorder, and cancers. However, nearly all conventional drug delivery system (DDS) nanocarriers utilize endocytosis for entering target cells; thus, the development of macrophage-targeting and phagocytosis-inducing DDS nanocarriers for treating these diseases is required. In this study, we developed a hepatitis B virus (HBV) envelope L particle (i.e., bio-nanocapsule (BNC)) outwardly displaying a tandem form of protein G-derived IgG Fc-binding domain and protein L-derived IgG Fab-binding domain (GL-BNC)...
April 16, 2018: Acta Biomaterialia
Masaharu Somiya, Qiushi Liu, Shun'ichi Kuroda
Nanomedicines often involve the use of nanocarriers as a delivery system for drugs or genes for maximizing the therapeutic effect and/or minimizing the adverse effect. From drug administration to therapeutic activity, nanocarriers must evade the host's immune system, specifically and efficiently target and enter the cell, and release their payload into the cell cytoplasm by endosomal escape. These processes constitute the early infection stage of viruses. Viruses are a powerful natural nanomaterial for the efficient delivery of genetic information by sophisticated mechanisms...
2017: Nanotheranostics
Joohee Jung, Masaharu Somiya, Seong-Yun Jeong, Eun Kyung Choi, Shun'ichi Kuroda
Bio-nanocapsules (BNCs) consisting of hepatitis B virus surface antigen (HBsAg) L proteins and phospholipids are used as efficient non-viral carriers for liver-specific delivery of genes and drugs. Considering the administration to HB vaccinees and HB patients, endogenous anti-HBsAg immunoglobulins (HBIGs) may reduce the delivery efficacy and prevent repetitive administration. Therefore, low immunogenic BNCs were generated by inserting two point mutations in the HBsAg L protein, which were found in HBV escape mutants...
November 22, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
Yuya Nishimura, Ryosuke Ezawa, Jun Ishii, Chiaki Ogino, Akihiko Kondo
The expression of epidermal growth factor receptor (EGFR) across a wide range of tumor cells has attracted attention for use as a tumor marker in drug delivery systems. Therefore, binding molecules with the ability to target EGFR have been developed. Among them, we focused on affibodies that are binding proteins derived from staphylococcal protein A. By displaying affibody (ZEGFR ) binding to EGFR on the surface of a bio-nanocapsule (BNC) derived from a hepatitis B virus (HBV), we developed an altered BNC (ZEGFR -BNC) with a high specificity to EGFR-expressing cells...
January 15, 2017: Bioorganic & Medicinal Chemistry Letters
Masumi Iijima, Shun'ichi Kuroda
Immunosensing is a widely used technique that detects the interactions between antibodies and antigens such as biochemical markers, pathogens, allergens, and tumor-associated antigens. Since target antigens are often of high molecular mass and their binding affinities are sometimes weak, the spatial arrangement of immunoglobulin Gs (IgGs) on immunosensing probes should be optimized by presenting them in as close-packed a manner as possible and reducing steric hindrance around the antigen-binding Fv regions...
March 15, 2017: Biosensors & Bioelectronics
Qiushi Liu, Masaharu Somiya, Shun'ichi Kuroda
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...
October 14, 2016: World Journal of Gastroenterology: WJG
Masaharu Somiya, Qiushi Liu, Nobuo Yoshimoto, Masumi Iijima, Kenji Tatematsu, Tadashi Nakai, Toshihide Okajima, Kazuyuki Kuroki, Keiji Ueda, Shun'ichi Kuroda
Sodium taurocholate cotransporting polypeptide (NTCP) was recently discovered as a hepatitis B virus (HBV) receptor, however, the detailed mechanism of HBV entry is not yet fully understood. We investigated the cellular entry pathway of HBV using recombinant HBV surface antigen L protein particles (bio-nanocapsules, BNCs). After the modification of L protein in BNCs with myristoyl group, myristoylated BNCs (Myr-BNCs) were found to bind to NTCP in vitro, and inhibit in vitro HBV infection competitively, suggesting that Myr-BNCs share NTCP-dependent infection machinery with HBV...
October 2016: Virology
Shinji Takamatsu, Mayuka Shimomura, Yoshihiro Kamada, Haruka Maeda, Tomoaki Sobajima, Hayato Hikita, Masumi Iijima, Yuta Okamoto, Ryo Misaki, Kazuhito Fujiyama, Shushi Nagamori, Yoshikatsu Kanai, Tetsuo Takehara, Keiji Ueda, Shun'ichi Kuroda, Eiji Miyoshi
The functions of cell surface proteins, such as growth factor receptors and virus/bacteria-entry receptors, can be dynamically regulated by oligosaccharide modifications. In the present study, we investigated the involvement of glycosylation in hepatitis B virus (HBV) entry into hepatoma cells. Infection of oligosaccharide-remodeling hepatoma cells with a pseudo virus of HBV, bio-nanocapsule (BNC), was evaluated by flow cytometry and confocal microscopy. Among various experiments using several hepatoma cells, marked difference was observed between Huh6 cells and HB611 cells, which were established by HBV gene transfection into hepatoma cells...
June 21, 2016: Glycobiology
Qiushi Liu, Masaharu Somiya, Naohiko Shimada, Wakako Sakamoto, Nobuo Yoshimoto, Masumi Iijima, Kenji Tatematsu, Tadashi Nakai, Toshihide Okajima, Atsushi Maruyama, Shuńichi Kuroda
A hollow nanoparticle known as a bio-nanocapsule (BNC) consisting of hepatitis B virus (HBV) envelope L protein and liposome (LP) can encapsulate drugs and genes and thereby deliver them in vitro and in vivo to human hepatic tissues, specifically by utilizing the HBV-derived infection machinery. Recently, we identified a low pH-dependent fusogenic domain at the N-terminal part of the pre-S1 region of the HBV L protein (amino acid residues 9 to 24; NPLGFFPDHQLDPAFG), which shows membrane destabilizing activity (i...
May 27, 2016: Biochemical and Biophysical Research Communications
Masumi Iijima, Nobuo Yoshimoto, Tomoaki Niimi, Andrés D Maturana, Shun'ichi Kuroda
Mammalian receptors are recognized as target molecules for drug discovery, and chemical libraries have been screened for both potential antagonists and agonists mainly by ligand-binding assays using immobilized receptors. A bio-nanocapsule (BNC) of approximately 30 nm that displays a tandem form of the protein A-derived immunoglobulin G (IgG) Fc-binding Z domains (denoted as ZZ-BNC) has been developed for both clustering and oriented immobilization of IgGs on the solid phase of immunosensors. In this study, human IgG1 Fc-fused vascular endothelial growth factor (VEGF) receptor was immobilized through ZZ-BNC on the sensor chip of quartz crystal microbalance (ZZ-BNC-coating)...
June 2016: Biotechnology Journal
Kenji Tatematsu, Masumi Iijima, Nobuo Yoshimoto, Tadashi Nakai, Toshihide Okajima, Shun'ichi Kuroda
UNLABELLED: The bio-nanocapsule (BNC) is an approximately 30-nm particle comprising the hepatitis B virus (HBV) envelope L protein and a lipid bilayer. The L protein harbors the HBV-derived infection machinery; therefore, BNC can encapsulate payloads such as drugs, nucleic acids, and proteins and deliver them into human hepatocytes specifically in vitro and in vivo. To diversify the possible functions of BNC, we generated ZZ-BNC by replacing the domain indispensable for the human hepatotrophic property of BNC (N-terminal region of L protein) with the tandem form of the IgG Fc-binding Z domain of Staphylococcus aureus protein A...
April 15, 2016: Acta Biomaterialia
Masaharu Somiya, Yasuo Sasaki, Takashi Matsuzaki, Qiushi Liu, Masumi Iijima, Nobuo Yoshimoto, Tomoaki Niimi, Andrés Daniel Maturana, Shun'ichi Kuroda
Bio-nanocapsules (BNCs) are a hollow nanoparticle consisting of about 100-nm liposome (LP) embedding about 110 molecules of hepatitis B virus (HBV) surface antigen (HBsAg) L protein as a transmembrane protein. Owing to the human hepatocyte-recognizing domains on the N-terminal region (pre-S1 region), BNCs have recently been shown to attach and enter into human hepatic cells using the early infection mechanism of HBV. Since BNCs could form a complex with an LP containing various drugs and genes, BNC-LP complexes have been used as a human hepatic cell-specific drug and gene-delivery system in vitro and in vivo...
August 28, 2015: Journal of Controlled Release: Official Journal of the Controlled Release Society
Xiaobin Xu, Kwanoh Kim, Chao Liu, Donglei Fan
In this work, we introduce the history and mechanisms of surface enhanced Raman scattering (SERS), discuss various techniques for fabrication of state-of-the-art SERS substrates, and review recent work on robotizing plasmonic nanoparticles, especially, the efforts we made on fabrication, characterization, and robotization of Raman nanosensors by design. Our nanosensors, consisting of tri-layer nanocapsule structures, are ultrasensitive, well reproducible, and can be robotized by either electric or magnetic tweezers...
2015: Sensors
Mai Mouslmani, Kamal H Bouhadir, Digambara Patra
Poly (9-(2-diallylaminoethyl)adenine HCl-co-sulfur dioxide) (Poly A) deposited on silica nanoparticles self-assembles to form hierarchically ordered nanocapsules. These nanocapsules can be conjugated with curcumin. The curcumin-conjugated nanocapsules are found to be spherical in size and their size ranges between 200 and 600 nm. We found that curcumin conjugated with silica nanoparticles marginally shows a selectivity (∼20%) for guanine over adenine, cytosine, thymine and uracil, but this selectivity is extraordinarily amplified to more than 500% in curcumin-conjugated nanocapsules prepared from the above procedure...
June 15, 2015: Biosensors & Bioelectronics
Yu Zhang, Benedict You Wei Hsu, Changliang Ren, Xu Li, John Wang
Synergistically combining the merits of silica (e.g., mechanical robustness, biocompatibility and great versatility in surface functionalization) and capsular configurations (e.g., a large inner cavity, low density and favourable colloidal properties), silica-based nanocapsules (SNCs) with a size cutoff of ∼100 nm have gained growing interest in encapsulating bioactive molecules for bioimaging and controlled delivery applications. Within this context, this review provides a comprehensive overview of the synthetic strategies, structural control and biomedical applications of SNCs...
January 7, 2015: Chemical Society Reviews
David Wibowo, Chun-Xia Zhao, Anton P J Middelberg
A novel, bio-inspired templating platform technology is reported for the synthesis of biocompatible oil-core silica-shell nanocapsules with tunable shell thickness by utilizing a designed bifunctional peptide. Furthermore, facile encapsulation of an active molecule and its sustained release are demonstrated.
October 7, 2014: Chemical Communications: Chem Comm
Kei Shimoda, Manabu Hamada, Masaharu Seno, Tadakatsu Mandai, Hiroki Hamada
Chemo-enzymatic synthesis of glycolyl-ester-linked taxol-glucose conjugate, ie, 7-glycolyltaxol 2″-O-α-D-glucoside, was achieved by using α-glucosidase as a biocatalyst. The water-solubility of 7-glycolyltaxol 2″-O-α-D-glucoside (21 μM) was 53 fold higher than that of taxol. The hepatitis B virus envelope L particles (bio-nanocapsules) are effective for delivering 7-glycolyltaxol 2″-O-α-D-glucoside to human hepatocellular carcinoma NuE cells.
2012: Biochemistry Insights
Qi Wang, Peifeng Liu, Ying Sun, Heng Wu, Xiaoyu Li, Yourong Duan, Zhirong Zhang
Pluronic-poly[alpha-(4-aminobutyl)-1-glycolic acid] (Pluronic-PAGA) with different types of Pluronic, the different molecule weight of PAGA, and the different molar ratios of Pluronic to PAGA were synthesized. These materials were bio-degradable, amphiphilic, could be degraded into non-toxic small molecules and could be used to carry drugs. 5-Fluorouracil (5-Fu) loaded Pluronic-PAGA micelle-like nanoparticles (5-Fu loaded P-PAGA NPs) were prepared by a simple self-assembly method, and characterized by dynamic light scattering, transmission electron microscope...
July 2014: Journal of Nanoscience and Nanotechnology
Jeong Yu Lee, Dong Heon Nam, Mi Hwa Oh, Youngsun Kim, Hyung Seok Choi, Duk Young Jeon, Chan Beum Park, Yoon Sung Nam
We introduce shell cross-linked protein/quantum dot (QD) hybrid nanocapsules as a serum-stable systemic delivery nanocarrier for tumor-targeted in vivo bio-imaging applications. Highly luminescent, heavy-metal-free Cu0.3InS2/ZnS (CIS/ZnS) core-shell QDs are synthesized and mixed with amine-reactive six-armed poly(ethylene glycol) (PEG) in dichloromethane. Emulsification in an aqueous solution containing human serum albumin (HSA) results in shell cross-linked nanocapsules incorporating CIS/ZnS QDs, exhibiting high luminescence and excellent dispersion stability in a serum-containing medium...
May 2, 2014: Nanotechnology
Yuya Nishimura, Koichi Takeda, Ryosuke Ezawa, Jun Ishii, Chiaki Ogino, Akihiko Kondo
BACKGROUND: An affibody-displaying bio-nanocapsule (ZHER2-BNC) with a hepatocyte specificity derived from hepatitis B virus (HBV) was converted into an affibody, ZHER2, that recognizes HER2 receptors. This affibody was previously reported to be the result of the endocytosis-dependent specific uptake of proteins and siRNA into target cancer cells. To assist the endosomal escape of inclusions, a helper lipid with pH-sensitive fusogenic ability (1,2-dioleoyl-sn-glycero-3-phos phoethanolamine; DOPE) was conjugated with a ZHER2-BNC...
2014: Journal of Nanobiotechnology
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