New packaging method of mycobacterial cell wall using octaarginine-modified liposomes: enhanced uptake by and immunostimulatory activity of dendritic cells. 2007

Atthachai Homhuan, and Kentaro Kogure, and Hideyuki Akaza, and Shiroh Futaki, and Takashi Naka, and Yukiko Fujita, and Ikuya Yano, and Hideyoshi Harashima
Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo, Hokkaido, Japan.

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.

UI MeSH Term Description Entries
D008055 Lipids A generic term for fats and lipoids, the alcohol-ether-soluble constituents of protoplasm, which are insoluble in water. They comprise the fats, fatty oils, essential oils, waxes, phospholipids, glycolipids, sulfolipids, aminolipids, chromolipids (lipochromes), and fatty acids. (Grant & Hackh's Chemical Dictionary, 5th ed) Lipid
D008081 Liposomes Artificial, single or multilaminar vesicles (made from lecithins or other lipids) that are used for the delivery of a variety of biological molecules or molecular complexes to cells, for example, drug delivery and gene transfer. They are also used to study membranes and membrane proteins. Niosomes,Transferosomes,Ultradeformable Liposomes,Liposomes, Ultra-deformable,Liposome,Liposome, Ultra-deformable,Liposome, Ultradeformable,Liposomes, Ultra deformable,Liposomes, Ultradeformable,Niosome,Transferosome,Ultra-deformable Liposome,Ultra-deformable Liposomes,Ultradeformable Liposome
D008297 Male Males
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D009163 Mycobacterium bovis The bovine variety of the tubercle bacillus. It is called also Mycobacterium tuberculosis var. bovis. BCG,Calmette-Guerin Bacillus
D009842 Oligopeptides Peptides composed of between two and twelve amino acids. Oligopeptide
D010316 Particle Size Relating to the size of solids. Particle Sizes,Size, Particle,Sizes, Particle
D010713 Phosphatidylcholines Derivatives of PHOSPHATIDIC ACIDS in which the phosphoric acid is bound in ester linkage to a CHOLINE moiety. Choline Phosphoglycerides,Choline Glycerophospholipids,Phosphatidyl Choline,Phosphatidyl Cholines,Phosphatidylcholine,Choline, Phosphatidyl,Cholines, Phosphatidyl,Glycerophospholipids, Choline,Phosphoglycerides, Choline
D002473 Cell Wall The outermost layer of a cell in most PLANTS; BACTERIA; FUNGI; and ALGAE. The cell wall is usually a rigid structure that lies external to the CELL MEMBRANE, and provides a protective barrier against physical or chemical agents. Cell Walls,Wall, Cell,Walls, Cell
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell

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