Multifunctional Envelope-Type Nano Device: Evolution from Nonselective to Active Targeting System.
A paradigm shift has occurred in the field of drug delivery systems (DDS), one being intracellular targeting, and the other, active targeting. An important aspect of intracellular targeting involves delivering nucleic acids such as siRNA/pDNA rather than small molecular compounds, since the mechanism responsible for their entering a target cell is usually via endocytosis, and the efficiency of endosomal escape is a critical factor in determining the functional activities of siRNA/pDNA. A multifunctional envelope-type nano device (MEND) was developed to control the intracellular trafficking of nano carriers containing siRNA/pDNA. An octaarginine (R8) modified MEND was developed to achieve this. Considerable progress has been made in active targeting to selective tissue vasculature such as tumor, adipose tissue, and the lung where endothelial barrier is tight against nanoparticles with diameters larger than 50 nm. A dual-ligand system is proposed to enhance active targeting ability by virtue of a synergistic interaction between a selective ligand and a cell penetrating ligand. Prohibitin targeted nanoparticles (PTNP) were developed to target endothelial cells in adipose tissue, which deliver apoptotic peptides/proteins to the adipose vasculature. Lung endothelial cells can be targeted by means of the GALA peptide, which is usually used to enhance endosomal escape. These active targeting systems can induce pharmacological effects in in vivo conditions. Finally, a novel strategy for producing an original ligand has been developed, especially for the tumor vasculature. This progress in DDS promises to extend the area of nanomedicine as a breakthrough technology.
Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan 060-0812.
Yasuhiro
Y
Hayashi
Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan 060-0812.
Hiroto
H
Hatakeyama
Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan 060-0812.
Kazuaki
K
Kajimoto
Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan 060-0812.
Mamoru
M
Hyodo
Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan 060-0812.
Hidetaka
H
Akita
Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan 060-0812.
Hideyoshi
H
Harashima
D000818:Animals; D052157:Aptamers, Nucleotide / Q000737:chemistry; D004247:DNA / Q000008:administration & dosage*; D016503:Drug Delivery Systems / Q000379:methods*; D018014:Gene Transfer Techniques; D006801:Humans; D008081:Liposomes / Q000737:chemistry; D049329:Nanostructures / Q000737:chemistry; D036103:Nanotechnology / Q000379:methods*; D009842:Oligopeptides / Q000737:chemistry; D010455:Peptides / Q000737:chemistry; D004364:Pharmaceutical Preparations / Q000008:administration & dosage*; D010957:Plasmids / Q000008:administration & dosage*; D034741:RNA, Small Interfering / Q000008:administration & dosage*
D052157:Aptamers, Nucleotide; D008081:Liposomes; D009842:Oligopeptides; D010455:Peptides; D004364:Pharmaceutical Preparations; D034741:RNA, Small Interfering; C448619:octaarginine; C066951:GALA peptide; D004247:DNA