PMID- 22591855 OWN - NLM STAT- MEDLINE DCOM- 20121210 LR - 20120529 IS - 1464-3391 (Electronic) IS - 0968-0896 (Linking) VI - 20 IP - 12 DP - 2012 Jun 15 TI - Targeting of polyplex to human hepatic cells by bio-nanocapsules, hepatitis B virus surface antigen L protein particles. PG - 3873-9 LID - 10.1016/j.bmc.2012.04.031 [doi] AB - We have previously demonstrated that lipoplex, a complex of cationic liposomes and DNA, could be targeted to human hepatic cells in vitro and in vivo by conjugation with bio-nanocapsules (BNCs) comprising hepatitis B virus (HBV) surface antigen L protein particles. Because the BNC-lipoplex complexes were endowed with the human hepatic cell-specific infection machinery from HBV, the complexes showed excellent specific transfection efficiency in human hepatic cells. In this study, we have found that polyplex (a complex of polyethyleneimine (PEI) and DNA) could form stable complexes with BNCs spontaneously. The diameter and zeta-potential of BNC-polyplex complexes are about 240 nm and +3.54 mV, respectively, which make them more suitable for in vivo use than polyplex alone. BNC-polyplex complexes with an N/P ratio (the molar ratio of the amine group of PEI to the phosphate group of DNA) of 40 showed excellent transfection efficiency in human hepatic cells. When acidification of endosomes was inhibited by bafilomycin A1, the complexes showed higher transfection efficiency than polyplex itself, strongly suggesting that the complexes escaped from endosomes by both fusogenic activity of BNCs and proton sponge activity of polyplex. Furthermore, the cytotoxicity is comparable to that of polyplex of the same N/P value. Thus, BNC-polyplex complexes would be a promising gene delivery carrier for human liver-specific gene therapy. CI - Copyright (c) 2012 Elsevier Ltd. All rights reserved. FAU - Somiya, Masaharu AU - Somiya M AD - Department of Bioengineering Sciences, Graduate School of Bioagricultural Sciences, Nagoya University, Furo-cho, Chikusa, Nagoya 464-8601, Japan. FAU - Yoshimoto, Nobuo AU - Yoshimoto N FAU - Iijima, Masumi AU - Iijima M FAU - Niimi, Tomoaki AU - Niimi T FAU - Dewa, Takehisa AU - Dewa T FAU - Jung, Joohee AU - Jung J FAU - Kuroda, Shun'ichi AU - Kuroda S LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120421 PL - England TA - Bioorg Med Chem JT - Bioorganic & medicinal chemistry JID - 9413298 RN - 0 (Hepatitis B Surface Antigens) RN - 0 (Macrolides) RN - 88899-55-2 (bafilomycin A1) RN - 9002-98-6 (Polyethyleneimine) RN - 9007-49-2 (DNA) SB - IM MH - DNA/*chemistry MH - Dose-Response Relationship, Drug MH - Endosomes/drug effects MH - *Gene Transfer Techniques MH - Genetic Therapy MH - Hepatitis B Surface Antigens/*chemistry/metabolism MH - Hepatocytes/*metabolism MH - Humans MH - Macrolides/pharmacology MH - Nanoparticles/*chemistry MH - Organ Specificity MH - Particle Size MH - Polyethyleneimine/*chemistry/pharmacology MH - Tumor Cells, Cultured EDAT- 2012/05/18 06:00 MHDA- 2012/12/12 06:00 CRDT- 2012/05/18 06:00 PHST- 2012/02/09 00:00 [received] PHST- 2012/04/15 00:00 [revised] PHST- 2012/04/16 00:00 [accepted] PHST- 2012/05/18 06:00 [entrez] PHST- 2012/05/18 06:00 [pubmed] PHST- 2012/12/12 06:00 [medline] AID - S0968-0896(12)00315-X [pii] AID - 10.1016/j.bmc.2012.04.031 [doi] PST - ppublish SO - Bioorg Med Chem. 2012 Jun 15;20(12):3873-9. doi: 10.1016/j.bmc.2012.04.031. Epub 2012 Apr 21.