1. Overcoming the blood-brain barrier by Annexin A1-binding peptide to target brain tumours.
- Author
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Nonaka M, Suzuki-Anekoji M, Nakayama J, Mabashi-Asazuma H, Jarvis DL, Yeh JC, Yamasaki K, Akama TO, Huang CT, Campos AR, Nagaoka M, Sasai T, Kimura-Takagi I, Suwa Y, Yaegashi T, Shibata TK, Sugihara K, Nishizawa-Harada C, Fukuda M, and Fukuda MN
- Subjects
- Animals, Humans, Mice, Mice, Inbred C57BL, Mice, SCID, Peptides, Rats, Annexin A1 metabolism, Antineoplastic Agents pharmacology, Blood-Brain Barrier metabolism, Brain Neoplasms, Drug Carriers pharmacology
- 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.
- Published
- 2020
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