Cyclic RGD-linked polymeric micelles for targeted delivery of platinum anticancer drugs to glioblastoma through the blood-brain tumor barrier

Yutaka Miura, Tomoya Takenaka, Kazuko Toh, Shourong Wu, Hiroshi Nishihara, Mitsunobu Kano, Yasushi Ino, Takahiro Nomoto, Yu Matsumoto, Hiroyuki Koyama, Horacio Cabral, Nobuhiro Nishiyama, Kazunori Kataoka

Research output: Contribution to journalArticle

247 Citations (Scopus)

Abstract

Ligand-mediated drug delivery systems have enormous potential for improving the efficacy of cancer treatment. In particular, Arg-Gly-Asp peptides are promising ligand molecules for targeting αvβ3/ αvβ5 integrins, which are overexpressed in angiogenic sites and tumors, such as intractable human glioblastoma (U87MG). We here achieved highly efficient drug delivery to U87MG tumors by using a platinum anticancer drug-incorporating polymeric micelle (PM) with cyclic Arg-Gly-Asp (cRGD) ligand molecules. Intravital confocal laser scanning microscopy revealed that the cRGD-linked polymeric micelles (cRGD/m) accumulated rapidly and had high permeability from vessels into the tumor parenchyma compared with the PM having nontargeted ligand, "cyclic-Arg-Ala-Asp" (cRAD). As both cRGD/m-and cRAD-linked polymeric micelles have similar characteristics, including their size, surface charge, and the amount of incorporated drugs, it is likely that the selective and accelerated accumulation of cRGD/m into tumors occurred via an active internalization pathway, possibly transcytosis, thereby producing significant antitumor effects in an orthotopic mouse model of U87MG human glioblastoma.

Original languageEnglish
Pages (from-to)8583-8592
Number of pages10
JournalACS Nano
Volume7
Issue number10
DOIs
Publication statusPublished - Oct 22 2013

Fingerprint

Micelles
Platinum
blood
brain
Tumors
Brain
delivery
micelles
drugs
platinum
Blood
tumors
Ligands
Pharmaceutical Preparations
ligands
Molecules
Oncology
Surface charge
Drug delivery
Integrins

Keywords

  • block copolymer
  • cancer therapy
  • cRGD
  • drug delivery
  • integrin
  • polymeric micelle

ASJC Scopus subject areas

  • Engineering(all)
  • Materials Science(all)
  • Physics and Astronomy(all)

Cite this

Cyclic RGD-linked polymeric micelles for targeted delivery of platinum anticancer drugs to glioblastoma through the blood-brain tumor barrier. / Miura, Yutaka; Takenaka, Tomoya; Toh, Kazuko; Wu, Shourong; Nishihara, Hiroshi; Kano, Mitsunobu; Ino, Yasushi; Nomoto, Takahiro; Matsumoto, Yu; Koyama, Hiroyuki; Cabral, Horacio; Nishiyama, Nobuhiro; Kataoka, Kazunori.

In: ACS Nano, Vol. 7, No. 10, 22.10.2013, p. 8583-8592.

Research output: Contribution to journalArticle

Miura, Y, Takenaka, T, Toh, K, Wu, S, Nishihara, H, Kano, M, Ino, Y, Nomoto, T, Matsumoto, Y, Koyama, H, Cabral, H, Nishiyama, N & Kataoka, K 2013, 'Cyclic RGD-linked polymeric micelles for targeted delivery of platinum anticancer drugs to glioblastoma through the blood-brain tumor barrier', ACS Nano, vol. 7, no. 10, pp. 8583-8592. https://doi.org/10.1021/nn402662d
Miura, Yutaka ; Takenaka, Tomoya ; Toh, Kazuko ; Wu, Shourong ; Nishihara, Hiroshi ; Kano, Mitsunobu ; Ino, Yasushi ; Nomoto, Takahiro ; Matsumoto, Yu ; Koyama, Hiroyuki ; Cabral, Horacio ; Nishiyama, Nobuhiro ; Kataoka, Kazunori. / Cyclic RGD-linked polymeric micelles for targeted delivery of platinum anticancer drugs to glioblastoma through the blood-brain tumor barrier. In: ACS Nano. 2013 ; Vol. 7, No. 10. pp. 8583-8592.
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