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

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.

SUBMITTER: Yoneyama T 

PROVIDER: S-EPMC7809749 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature