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

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 t...

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Bibliographic Details
Published in:British journal of cancer 2020-11, Vol.123 (11), p.1633-1643
Main 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.
Format: Article
Language:English
Subjects:
631/67/1922
692/699/67/1059
Animal models
Animals
Annexin A1 - metabolism
Antineoplastic Agents - pharmacology
Biomedical and Life Sciences
Biomedicine
Blood-brain barrier
Blood-Brain Barrier - metabolism
Brain cancer
Brain Neoplasms
Brain tumors
Cancer Research
Cell culture
Chemiluminescence
Drug Carriers - pharmacology
Drug Resistance
Epidemiology
Humans
Immune response
Injection
Melanoma
Mice
Mice, Inbred C57BL
Mice, SCID
Molecular Medicine
Oncology
Peptides
Rats
Tumor cell lines
Tumors
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Summary: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.
ISSN:0007-0920
1532-1827
DOI:10.1038/s41416-020-01066-2