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Updated: Dec 9, 2025
Predicting In Vivo Payloads Delivery using a Blood-brain Tumor-barrier in a Dish
Published on: April 16, 2019
Overcoming the blood-brain barrier by Annexin A1-binding peptide to target brain tumours
Motohiro Nonaka1,2,3, Misa Suzuki-Anekoji1, Jun Nakayama4
1Cancer Center, Sanford-Burnham-Prebys Medical Discovery Institute, La Jolla, CA, 92037, USA.
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.
Insights
Intravenously injected IF7C(RR)-SN38 crosses the blood-brain barrier to suppress brain tumor growth in mice. Solutol HS15 formulation may enhance this effect through immune response.
Area of Science:
- Oncology
- Nanomedicine
- Pharmacology
Background:
- Annexin A1 is a specific marker on tumor vasculature.
- The IF7 antibody targets tumor vasculature via Annexin A1.
- This study investigates IF7's potential to cross the blood-brain barrier and eradicate brain tumors.
Purpose of the Study:
- To evaluate the efficacy of intravenously administered IF7C(RR)-SN38 in mouse models of brain tumors.
- To determine if IF7C(RR)-SN38 can overcome the blood-brain barrier.
- To assess the role of Solutol HS15 formulation in enhancing anti-tumor activity.
Main Methods:
- Dual-tumor models were established using luciferase-expressing melanoma (B16-Luc) or glioma (C6-Luc) cell lines in syngeneic or immunocompromised mice.
- Mice received daily intravenous injections of IF7C(RR)-SN38 at varying doses and formulations.
- Tumor growth was monitored using in vivo imaging systems (IVIS) based on chemiluminescence.
Main Results:
- Daily IF7C(RR)-SN38 administration suppressed tumor growth across different cell lines and mouse strains.
- Complete eradication of B16-Luc brain tumors was observed in C57BL/6 mice treated with Solutol HS15-formulated IF7C(RR)-SN38.
- The same formulation did not result in complete tumor disappearance in C6-Luc bearing nude mice.
Conclusions:
- IF7C(RR)-SN38 demonstrates the ability to cross the blood-brain barrier and inhibit brain tumor progression in preclinical models.
- The Solutol HS15 formulation of IF7C(RR)-SN38 may potentiate anti-tumor effects, potentially through an induced immune response.
