Density-tunable conjugation of cyclic RGD ligands with polyion complex vesicles for the neovascular imaging of orthotopic glioblastomas

Wataru Kawamura, Yutaka Miura, Daisuke Kokuryo, Kazuko Toh, Naoki Yamada, Takahiro Nomoto, Yu Matsumoto, Daiki Sueyoshi, Xueying Liu, Ichio Aoki, Mitsunobu Kano, Nobuhiro Nishiyama, Tsuneo Saga, Akihiro Kishimura, Kazunori Kataoka

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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 Vβ3 and vβ5 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 Vβ3 integrins.

Original languageEnglish
Article number035004
JournalScience and Technology of Advanced Materials
Volume16
Issue number3
DOIs
Publication statusPublished - Jun 1 2015

Fingerprint

Polyethylene glycols
Ligands
Imaging techniques
Magnetic resonance
Iron oxides
Tumors
Endothelial cells
Hemodynamics
Macromolecules
Integrins
Capsules
Microscopic examination
Tissue
Scanning
cyclic arginine-glycine-aspartic acid peptide
Lasers
Water

Keywords

  • cyclic RGD
  • drug delivery
  • glioblastoma
  • MRI (magnetic resonance imaging)
  • polymersome

ASJC Scopus subject areas

  • Materials Science(all)

Cite this

Density-tunable conjugation of cyclic RGD ligands with polyion complex vesicles for the neovascular imaging of orthotopic glioblastomas. / Kawamura, Wataru; Miura, Yutaka; Kokuryo, Daisuke; Toh, Kazuko; Yamada, Naoki; Nomoto, Takahiro; Matsumoto, Yu; Sueyoshi, Daiki; Liu, Xueying; Aoki, Ichio; Kano, Mitsunobu; Nishiyama, Nobuhiro; Saga, Tsuneo; Kishimura, Akihiro; Kataoka, Kazunori.

In: Science and Technology of Advanced Materials, Vol. 16, No. 3, 035004, 01.06.2015.

Research output: Contribution to journalArticle

Kawamura, W, Miura, Y, Kokuryo, D, Toh, K, Yamada, N, Nomoto, T, Matsumoto, Y, Sueyoshi, D, Liu, X, Aoki, I, Kano, M, Nishiyama, N, Saga, T, Kishimura, A & Kataoka, K 2015, 'Density-tunable conjugation of cyclic RGD ligands with polyion complex vesicles for the neovascular imaging of orthotopic glioblastomas', Science and Technology of Advanced Materials, vol. 16, no. 3, 035004. https://doi.org/10.1088/1468-6996/16/3/035004
Kawamura, Wataru ; Miura, Yutaka ; Kokuryo, Daisuke ; Toh, Kazuko ; Yamada, Naoki ; Nomoto, Takahiro ; Matsumoto, Yu ; Sueyoshi, Daiki ; Liu, Xueying ; Aoki, Ichio ; Kano, Mitsunobu ; Nishiyama, Nobuhiro ; Saga, Tsuneo ; Kishimura, Akihiro ; Kataoka, Kazunori. / Density-tunable conjugation of cyclic RGD ligands with polyion complex vesicles for the neovascular imaging of orthotopic glioblastomas. In: Science and Technology of Advanced Materials. 2015 ; Vol. 16, No. 3.
@article{fa9f8b555f764a5cb2d408a2bc4c6292,
title = "Density-tunable conjugation of cyclic RGD ligands with polyion complex vesicles for the neovascular imaging of orthotopic glioblastomas",
abstract = "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 Vβ3 and vβ5 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 Vβ3 integrins.",
keywords = "cyclic RGD, drug delivery, glioblastoma, MRI (magnetic resonance imaging), polymersome",
author = "Wataru Kawamura and Yutaka Miura and Daisuke Kokuryo and Kazuko Toh and Naoki Yamada and Takahiro Nomoto and Yu Matsumoto and Daiki Sueyoshi and Xueying Liu and Ichio Aoki and Mitsunobu Kano and Nobuhiro Nishiyama and Tsuneo Saga and Akihiro Kishimura and Kazunori Kataoka",
year = "2015",
month = "6",
day = "1",
doi = "10.1088/1468-6996/16/3/035004",
language = "English",
volume = "16",
journal = "Science and Technology of Advanced Materials",
issn = "1468-6996",
publisher = "IOP Publishing Ltd.",
number = "3",

}

TY - JOUR

T1 - Density-tunable conjugation of cyclic RGD ligands with polyion complex vesicles for the neovascular imaging of orthotopic glioblastomas

AU - Kawamura, Wataru

AU - Miura, Yutaka

AU - Kokuryo, Daisuke

AU - Toh, Kazuko

AU - Yamada, Naoki

AU - Nomoto, Takahiro

AU - Matsumoto, Yu

AU - Sueyoshi, Daiki

AU - Liu, Xueying

AU - Aoki, Ichio

AU - Kano, Mitsunobu

AU - Nishiyama, Nobuhiro

AU - Saga, Tsuneo

AU - Kishimura, Akihiro

AU - Kataoka, Kazunori

PY - 2015/6/1

Y1 - 2015/6/1

N2 - 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 Vβ3 and vβ5 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 Vβ3 integrins.

AB - 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 Vβ3 and vβ5 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 Vβ3 integrins.

KW - cyclic RGD

KW - drug delivery

KW - glioblastoma

KW - MRI (magnetic resonance imaging)

KW - polymersome

UR - http://www.scopus.com/inward/record.url?scp=84937884231&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84937884231&partnerID=8YFLogxK

U2 - 10.1088/1468-6996/16/3/035004

DO - 10.1088/1468-6996/16/3/035004

M3 - Article

AN - SCOPUS:84937884231

VL - 16

JO - Science and Technology of Advanced Materials

JF - Science and Technology of Advanced Materials

SN - 1468-6996

IS - 3

M1 - 035004

ER -