title: New packaging method of mycobacterial cell wall using octaarginine-modified liposomes: enhanced uptake by and immunostimulatory activity of dendritic cells.
abstract: Despite the potential of mycobacterial cell wall (CW) components to serve as immunotherapeutic agents, this application is hampered by the molecules' unfavorable physicochemical properties, such as its high molecular weight, poor solubility and negatively charged nature. Here we describe a new mycobacterial CW delivery system that uses an efficient and simple packaging method. This is achieved by incorporating mycobacterial CW into liposomes and attaching arginine octamers (R8) to the liposome surface. R8-modified liposomes improve the uptake of mycobacterial CW by dendritic cells (DC) and enhance its immunostimulatory activity. High R8 surface density promoted high levels of mycobacterial CW uptake by DC compared to low density R8-modified liposomes. Maturation markers (CD80, CD86, MHC Class II molecules) showed significantly enhanced expression on DC pulsed with high density R8-modified liposomes containing mycobacterial CW. Moreover, R8-modified liposomes with mycobacterial CW incorporated induced production of IL-12 p40 by DC, at levels similar to those produced by lipopolysaccharide-pulsed DC. We assert that R8-modified liposomes with mycobacterial CW incorporated should have tremendous potential as immune-potentiating agents.
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo, Hokkaido, Japan.
authors.forename: Atthachai
authors.initials: A
authors.lastname: Homhuan
authors.forename: Kentaro
authors.initials: K
authors.lastname: Kogure
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Akaza
authors.forename: Shiroh
authors.initials: S
authors.lastname: Futaki
authors.forename: Takashi
authors.initials: T
authors.lastname: Naka
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Fujita
authors.forename: Ikuya
authors.initials: I
authors.lastname: Yano
authors.forename: Hideyoshi
authors.initials: H
authors.lastname: Harashima
mesh_terms: D000818:Animals; D018122:B7-1 Antigen / Q000032:analysis; D051940:B7-2 Antigen / Q000032:analysis; D019496:Cancer Vaccines / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D002473:Cell Wall / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D002626:Chemistry, Pharmaceutical; D002784:Cholesterol / Q000737:chemistry; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D004339:Drug Compounding; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D053762:Interleukin-12 Subunit p40 / Q000378:metabolism; D008055:Lipids / Q000737:chemistry*; D008081:Liposomes; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009163:Mycobacterium bovis / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism*; D010316:Particle Size; D010713:Phosphatidylcholines / Q000737:chemistry; D012995:Solubility
chemical_list: D018122:B7-1 Antigen; D051940:B7-2 Antigen; D019496:Cancer Vaccines; C497965:Cd86 protein, mouse; D000949:Histocompatibility Antigens Class II; D053762:Interleukin-12 Subunit p40; D008055:Lipids; D008081:Liposomes; D009842:Oligopeptides; D010713:Phosphatidylcholines; C448619:octaarginine; D002784:Cholesterol