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

Autor:	Yoneyama, Tohru, Hatakeyama, Shingo, Sutoh-Yoneyama, Mihoko, Yoshiya, Taku, Uemura, Tsuyoshi, Ishizu, Takehiro, Suzuki, Minoru, Hachinohe, Shingo, Ishiyama, Shintaro, Nonaka, Motohiro, Fukuda, Michiko N., Ohyama, Chikara
Předmět:	BORON-neutron capture therapy BLADDER cancer BISPHENOLS TUMOR growth PHENYLALANINE metabolism BLADDER tumors CANCER cell culture PHENYLALANINE BORON compounds ANIMAL experimentation APOPTOSIS CELL physiology PATHOLOGIC neovascularization CALCIUM-binding proteins RADIOTHERAPY MOLECULAR structure PEPTIDES MICE ANIMALS METABOLISM
Zdroj:	BMC Cancer; 1/14/2021, Vol. 21 Issue 1, p1-15, 15p
Abstrakt:	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. [ABSTRACT FROM AUTHOR]
Databáze:	Complementary Index
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