PMID- 22848163 OWN - NLM STAT- MEDLINE DCOM- 20130221 LR - 20211021 IS - 1178-2013 (Electronic) IS - 1176-9114 (Print) IS - 1176-9114 (Linking) VI - 7 DP - 2012 TI - Engineered hepatitis B virus surface antigen L protein particles for in vivo active targeting of splenic dendritic cells. PG - 3341-50 LID - 10.2147/IJN.S32813 [doi] AB - Dendritic cells (DCs) are key regulators of adaptive T-cell responses. By capturing exogenous antigens and presenting antigen-derived peptides via major histocompatibility complex molecules to naive T cells, DCs induce antigen-specific immune responses in vivo. In order to induce effective host immune responses, active delivery of exogenous antigens to DCs is considered important for future vaccine development. We recently generated bionanocapsules (BNCs) consisting of hepatitis B virus surface antigens that mediate stringent in vivo cell targeting and efficient endosomal escape, and after the fusion with liposomes (LP) containing therapeutic materials, the BNC-LP complexes deliver them to human liver-derived tissues in vivo. BNCs were further modified to present the immunoglobulin G (IgG) Fc-interacting domain (Z domain) derived from Staphylococcus aureus protein A in tandem. When mixed with IgGs, modified BNCs (ZZ-BNCs) displayed the IgG Fv regions outwardly for efficient binding to antigens in an oriented-immobilization manner. Due to the affinity of the displayed IgGs, the IgG-ZZ-BNC complexes accumulated in specific cells and tissues in vitro and in vivo. After mixing ZZ-BNCs with antibodies against DCs, we used immunocytochemistry to examine which antibodies delivered ZZ-BNCs to mouse splenic DCs following intravenous injection of the ZZ-BNCs. ZZ-BNCs displaying anti-CD11c monoclonal antibodies (alpha-CD11c-ZZ-BNCs) were found to accumulate with approximately 62% of splenic DCs, and reside within some of them. After the fusion with liposomes containing antigens, the alpha-CD11c-ZZ-BNCs could elicit the respective antibodies more efficiently than other nontargeting control vaccines, suggesting that this DC-specific nanocarrier is promising for future vaccines. FAU - Matsuo, Hidenori AU - Matsuo H AD - Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan. FAU - Yoshimoto, Nobuo AU - Yoshimoto N FAU - Iijima, Masumi AU - Iijima M FAU - Niimi, Tomoaki AU - Niimi T FAU - Jung, Joohee AU - Jung J FAU - Jeong, Seong-Yun AU - Jeong SY FAU - Choi, Eun Kyung AU - Choi EK FAU - Sewaki, Tomomitsu AU - Sewaki T FAU - Arakawa, Takeshi AU - Arakawa T FAU - Kuroda, Shun'ichi AU - Kuroda S LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120703 PL - New Zealand TA - Int J Nanomedicine JT - International journal of nanomedicine JID - 101263847 RN - 0 (Antibodies, Monoclonal) RN - 0 (Antigens, Viral) RN - 0 (Bacterial Vaccines) RN - 0 (Hepatitis B Surface Antigens) RN - 0 (L protein, hepatitis B virus) RN - 0 (Liposomes) RN - 0 (Nanocapsules) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Staphylococcal Protein A) RN - 0 (Viral Envelope Proteins) RN - 0 (Viral Proteins) SB - IM MH - Animals MH - Antibodies, Monoclonal/metabolism MH - Antigens, Viral/immunology MH - Bacterial Vaccines/chemistry/immunology/metabolism/pharmacokinetics MH - Dendritic Cells/*metabolism MH - Encephalitis Virus, Japanese/immunology MH - Female MH - Hepatitis B Surface Antigens/chemistry/*metabolism MH - Liposomes/chemistry/immunology/metabolism/pharmacokinetics MH - Mice MH - Mice, Inbred BALB C MH - Nanocapsules/administration & dosage/*chemistry MH - Recombinant Fusion Proteins/chemistry/immunology/*metabolism/pharmacokinetics MH - Spleen/cytology MH - Staphylococcal Protein A/chemistry/genetics/metabolism MH - Tissue Distribution MH - Viral Envelope Proteins/chemistry/*metabolism MH - Viral Proteins/immunology PMC - PMC3405891 OTO - NOTNLM OT - ZZ domain OT - drug-delivery system OT - gene-delivery system OT - liposomes OT - protein A OT - vaccine EDAT- 2012/08/01 06:00 MHDA- 2013/02/22 06:00 PMCR- 2012/07/03 CRDT- 2012/08/01 06:00 PHST- 2012/08/01 06:00 [entrez] PHST- 2012/08/01 06:00 [pubmed] PHST- 2013/02/22 06:00 [medline] PHST- 2012/07/03 00:00 [pmc-release] AID - ijn-7-3341 [pii] AID - 10.2147/IJN.S32813 [doi] PST - ppublish SO - Int J Nanomedicine. 2012;7:3341-50. doi: 10.2147/IJN.S32813. Epub 2012 Jul 3.