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.
Subject(s)
Annexin A1/metabolism , Boron Compounds/administration & dosage , Boron Neutron Capture Therapy/methods , Neovascularization, Pathologic/radiotherapy , Peptide Fragments/metabolism , Phenylalanine/analogs & derivatives , Urinary Bladder Neoplasms/radiotherapy , Animals , Apoptosis , Boron Compounds/chemistry , Boron Compounds/metabolism , Cell Proliferation , Female , Humans , Mice , Mice, Inbred BALB C , Mice, Inbred C3H , Mice, Nude , Neovascularization, Pathologic/metabolism , Neovascularization, Pathologic/pathology , Phenylalanine/administration & dosage , Phenylalanine/chemistry , Phenylalanine/metabolism , Tumor Cells, Cultured , Urinary Bladder Neoplasms/metabolism , Urinary Bladder Neoplasms/pathology , Xenograft Model Antitumor AssaysABSTRACT
A simple and robust approach to visualization of continuous wave terahertz (CW-THz) light would open up opportunities to couple physical phenomena that occur at fundamentally different energy scales. Here we demonstrate how nanoscale cages of Ca12Al14O33 crystal enable conversion of CW-THz radiation to visible light. These crystallographic cages are partially occupied with weakly bonded oxygen ions and give rise to a narrow conduction band that can be populated with localized, yet mobile electrons. CW-THz light excites a nearly stand-alone rattling motion of the encaged oxygen species, which promotes electron transfer from them to the neighboring vacant cages. When the power of CW-THz light reaches tens of watts, the coupling between forced rattling in the confined space, electronic excitation and ionization of oxygen species, and corresponding recombination processes result in emission of bright visible light.
