@article{oai:repo.qst.go.jp:00047453,
 author = {Kawamura, Wataru and Miura, Yutaka and Kokuryo, Daisuke and Toh, Kazuko and Yamada, Naoki and Nomoto, Takahiro and Matsumoto, Yu and Daiki, Sueyoshi and Liu, Xueying and Aoki, Ichio and Nobuhiro, Nishiyama and Saga, Tsuneo and Kishimura, Akihiro and Kataoka, Kazunori and 國領 大介 and 青木 伊知男 and 佐賀 恒夫},
 journal = {Science and Technology of Advanced Materials},
 month = {May},
 note = {Introduction of ligands into 100 nm scaled hollow capsules has great potential for diagnostic and therapeutic applications in drug delivery systems. Polyethylene glycol-conjugated (PEGylated) polyion complex vesicles (PICsomes) are promising hollow nano-capsules that can survive for long periods in the blood circulation and can be used to deliver water-soluble macromolecules to target tissues. In this study, cyclic RGD (cRGD) peptide, which is specifically recognized by αVβ3 and αvβ5 integrins that are expressed at high levels in the neovascular system, was conjugated onto the distal end of PEG strands on PICsomes for active neovascular targeting. Density-tunable cRGD-conjugation was achieved using PICsomes with definite fraction of end-functionalized PEG, to substitute 20, 40, and 100% of PEG distal end of the PICsomes to cRGD moieties. Compared with control-PICsomes without cRGD, cRGD-PICsomes exhibited increased uptake into human umbilical vein endothelial cells. Intravital confocal laser scanning microscopy revealed that the 40%-cRGD-PICsomes accumulated mainly in the tumor neovasculature and remained in the perivascular region even after 24 h. Furthermore, we prepared superparamagnetic iron oxide (SPIO)-loaded cRGD-PICsomes for magnetic resonance imaging (MRI) and successfully visualized the neovasculature in an orthotopic glioblastoma model, which suggests that SPIO-loaded cRGD-PICsomes might be useful as a MRI contrast reagent for imaging of the tumor microenvironment, including neovascular regions that overexpress αVβ3 integrins.},
 pages = {035004-1--035004-13},
 title = {Density-tunable conjugation of cyclic RGD ligands with polyion complex vesicles for the neovascular imaging of orthotopic glioblastomas},
 volume = {16},
 year = {2015}
}