Low immunogenic bio-nanocapsule based on hepatitis B virus escape mutants
| Autor: | Joohee Jung, Seong-Yun Jeong, Shun'ichi Kuroda, Masaharu Somiya, Eun Kyung Choi |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Hepatitis B virus HBsAg Carcinoma Hepatocellular Mutant Biomedical Engineering Pharmaceutical Science Medicine (miscellaneous) Bioengineering medicine.disease_cause Mice 03 medical and health sciences Drug Delivery Systems 0302 clinical medicine Nanocapsules Viral Envelope Proteins Tumor Cells Cultured medicine Animals Humans General Materials Science Cationic liposome Gene Mice Inbred BALB C Hepatitis B Surface Antigens biology Chemistry Immunogenicity Point mutation Liver Neoplasms Hepatitis B Antibodies Neutralizing Xenograft Model Antitumor Assays Virology 030104 developmental biology 030220 oncology & carcinogenesis Liposomes Mutation biology.protein Molecular Medicine Antibody |
| Zdroj: | Nanomedicine: Nanotechnology, Biology and Medicine. 14:595-600 |
| ISSN: | 1549-9634 |
| Popis: | 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. Escape mutant-type BNC (emBNC) showed 50% lower HBIG binding capacity than that of parental BNC (wtBNC). It induced HBIG production to a lesser extent than that associated with wtBNC in BALB/c mice. The emBNC could accumulate into human hepatocyte-derived tumor in mice pre-treated with HBIGs. The complex of emBNC and cationic liposomes could deliver plasmid DNA to HepG2 cells efficiently in the presence of HBIGs. Thus, emBNC could evade HBIG-neutralizing antibodies, expanding the clinical utility of BNC-based nanomedicine. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect