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- Title
Overcoming the blood-brain barrier by Annexin A1-binding peptide to target brain tumours.
- Authors
Nonaka, Motohiro; Suzuki-Anekoji, Misa; Nakayama, Jun; Mabashi-Asazuma, Hideaki; Jarvis, Donald L.; Yeh, Jiunn-Chern; Yamasaki, Kazuhiko; Akama, Tomoya O.; Huang, Chun-Teng; Campos, Alexandre Rosa; Nagaoka, Masato; Sasai, Toshio; Kimura-Takagi, Itsuko; Suwa, Yoichi; Yaegashi, Takashi; Shibata, Toshiaki K.; Sugihara, Kazuhiro; Nishizawa-Harada, Chizuko; Fukuda, Minoru; Fukuda, Michiko N.
- Abstract
<bold>Background: </bold>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.<bold>Methods: </bold>(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.<bold>Results: </bold>(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.<bold>Conclusions: </bold>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.
- Subjects
DRUG delivery systems; RESEARCH; BLOOD-brain barrier; ANIMAL experimentation; RESEARCH methodology; ANTINEOPLASTIC agents; MEDICAL cooperation; EVALUATION research; BRAIN tumors; RATS; COMPARATIVE studies; RESEARCH funding; CALCIUM-binding proteins; MICE; PEPTIDES; PHARMACODYNAMICS
- Publication
British Journal of Cancer, 2020, Vol 123, Issue 11, p1633
- ISSN
0007-0920
- Publication type
journal article
- DOI
10.1038/s41416-020-01066-2