Tumor vasculature-targeted 10B delivery by an Annexin A1-binding peptide boosts effects of boron neutron capture therapy

BMC Cancer

Shingo Hachinohe¹  Motohiro Nonaka²  Mihoko Sutoh-Yoneyama³  Tohru Yoneyama⁴  Shingo Hatakeyama⁵  Chikara Ohyama⁵  Shintaro Ishiyama⁶  Minoru Suzuki⁷  Tsuyoshi Uemura⁸  Takehiro Ishizu⁸  Taku Yoshiya⁸  Michiko N. Fukuda⁹ 

[1] Aomori Prefecture Quantum Science Center (QSC);Department of Biological Chemistry, Human Health Sciences, Graduate School of Medicine, Kyoto University;Department of Cancer Immunology and Cell Biology, Oyokyo Kidney Research Institute;Department of Glycotechnology, Center for Advanced Medical Research, Hirosaki University Graduate School of Medicine;Department of Urology, Hirosaki University Graduate School of Medicine;Faculty of Science and Technology, Hirosaki University Graduate School of Science and Technology;Particle Radiation Oncology Research Center, Institute for Integrated Radiation and Nuclear Science (KURNS);Peptide Institute Inc.;Tumor Microenvironment and Cancer Immunology Program, NCI-Designated Cancer Center, Sanford Burnham Prebys Medical Discovery Institute;

关键词: Drug delivery;    Peptide;    Annexin A1;    Tumor vasculature;    Boron neutron capture therapy;   

DOI  :  10.1186/s12885-020-07760-x

来源: DOAJ

【 摘 要 】

Abstract Background p-Boronophenylalanine (10BPA) is a powerful 10B drug used in current clinical trials of BNCT. For BNCT to be successful, a high (500 mg/kg) dose of 10BPA must be administered over a few hours. Here, we report BNCT efficacy after rapid, ultralow-dose administration of either tumor vasculature-specific annexin A1-targeting IFLLWQR (IF7)-conjugated 10BPA or borocaptate sodium (10BSH). Methods (1) IF7 conjugates of either 10B drugs intravenously injected into MBT2 bladder tumor-bearing mice and biodistribution of 10B in tumors and normal organs analyzed by prompt gamma-ray analysis. (2) Therapeutic effect of IF7-10B drug-mediated BNCT was assessed by either MBT2 bladder tumor bearing C3H/He mice and YTS-1 tumor bearing nude mice. Results Intravenous injection of IF7C conjugates of either 10B drugs into MBT2 bladder tumor-bearing mice promoted rapid 10B accumulation in tumor and suppressed tumor growth. Moreover, multiple treatments at ultralow (10–20 mg/kg) doses of IF7-10B drug-mediated BNCT significantly suppressed tumor growth in a mouse model of human YTS-1 bladder cancer, with increased Anxa1 expression in tumors and infiltration by CD8-positive lymphocytes. Conclusions We conclude that IF7 serves as an efficient 10B delivery vehicle by targeting tumor tissues via the tumor vasculature and could serve as a relevant vehicle for BNCT drugs.

【 授权许可】

Unknown