Overcoming the blood–brain barrier by Annexin A1-binding peptide to target brain tumours

Motohiro Nonaka, Misa Suzuki-Anekoji, Jun Nakayama, Hideaki Mabashi-Asazuma, Donald L. Jarvis, Jiunn Chern Yeh, Kazuhiko Yamasaki, Tomoya O. Akama, Chun Teng Huang, Alexandre Rosa Campos, Masato Nagaoka, Toshio Sasai, Itsuko Kimura-Takagi, Yoichi Suwa, Takashi Yaegashi, Toshiaki K. Shibata, Kazuhiro Sugihara, Chizuko Nishizawa-Harada, Minoru Fukuda, Michiko N. Fukuda

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

Background: Annexin A1 is expressed specifically on the tumour vasculature surface. Intravenously injected IF7 targets tumour vasculature via annexin A1. We tested the hypothesis that IF7 overcomes the blood–brain barrier and that the intravenously injected IF7C(RR)-SN38 eradicates brain tumours in the mouse. Methods: (1) A dual-tumour model was generated by inoculating luciferase-expressing melanoma B16 cell line, B16-Luc, into the brain and under the skin of syngeneic C57BL/6 mice. IF7C(RR)-SN38 was injected intravenously daily at 7.0 μmoles/kg and growth of tumours was assessed by chemiluminescence using an IVIS imager. A similar dual-tumour model was generated with the C6-Luc line in immunocompromised SCID mice. (2) IF7C(RR)-SN38 formulated with 10% Solutol HS15 was injected intravenously daily at 2.5 μmoles/kg into two brain tumour mouse models: B16-Luc cells in C57BL/6 mice, and C6-Luc cells in nude mice. Results: (1) Daily IF7C(RR)-SN38 injection suppressed tumour growth regardless of cell lines or mouse strains. (2) Daily injection of Solutol-formulated IF7C(RR)-SN38 led into complete disappearance of B16-Luc brain tumour in C57BL/6 mice, whereas this did not occur in C6-Luc in nude mice. Conclusions: IF7C(RR)-SN38 crosses the blood–brain barrier and suppresses growth of brain tumours in mouse models. Solutol HS15-formulated IF7C(RR)-SN38 may have promoted an antitumour immune response.

Original languageEnglish
Pages (from-to)1633-1643
Number of pages11
JournalBritish Journal of Cancer
Volume123
Issue number11
DOIs
Publication statusPublished - 24-11-2020
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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