Therapeutic efficacy of boron neutron capture therapy mediated by boron-rich liposomes for oral cancer in the hamster cheek pouch model

Abstract

The application of boron neutron capture therapy (BNCT) mediated by liposomes containing 10 B-enriched polyhedral borane and carborane derivatives for the treatment of head and neck cancer in the hamster cheek pouch oral cancer model is presented. These liposomes are composed of an equimolar ratio of cholesterol and 1,2-distearoyl-sn-glycero-3-phosphocholine, incorporating K[nido-7-CH 3 (CH 2 ) 15 -7,8-C 2 B 9 H 11 ] (MAC) in the bilayer membrane while encapsulating the hydrophilic species Na 3 [ae-B 20 H 17 NH 3 ] (TAC) in the aqueous core. Unilamellar liposomes with a mean diameter of 83 nm were administered i.v. in hamsters. After 48 h, the boron concentration in tumors was 67 ± 16 ppm whereas the precancerous tissue contained 11 ± 6 ppm, and the tumor/normal pouch tissue boron concentration ratio was 10:1. Neutron irradiation giving a 5-Gy dose to precancerous tissue (corresponding to 21 Gy in tumor) resulted in an overall tumor response (OR) of 70% after a 4-wk posttreatment period. In contrast, the beam-only protocol gave an OR rate of only 28%. Once-repeated BNCT treatment with readministration of liposomes at an interval of 4, 6, or 8 wk resulted in OR rates of 70-88%, of which the complete response ranged from 37% to 52%. Because of the good therapeutic outcome, it was possible to extend the follow-up of BNCT treatment groups to 16 wk after the first treatment. No radiotoxicity to normal tissue was observed. A salient advantage of these liposomes was that only mild mucositis was observed in dose-limiting precancerous tissue with a sustained tumor response of 70-88%.oncology | cancer | boronated liposomes | BNCT | neutron radiation

Synthesis and Applications of Perfunctionalized Boron Clusters

“…133–137 In particular, many boron-encapsulated and boron-lipid liposomes have shown promising results in their ability to selectively deliver therapeutic quantities of 10 B atoms into tumor cells for effective BNCT. 138–146 …”

Advancements in Tumor Targeting Strategies for Boron Neutron Capture Therapy

“…administration (2 injections 24 h apart) of these liposomes into BALC/c mice containing EMT6 tumors (mouse mammary adenocarcinoma), a T/B ratio of 5.68 with a tumor boron concentration of 43 ppm was obtained 96 h post-injection. These liposomes have also shown promising potential in a hamster cheek pouch oral cancer model [81].…”

Histamine reduces boron neutron capture therapy‐induced mucositis in an oral precancer model

“…Carcinogenesis protocols induce premalignant and malignant changes that closely resemble spontaneous human oral mucosa lesions (Kreimann et al , ; Vairaktaris et al , ; Heber et al , ; Monti‐Hughes et al , ). We previously demonstrated BNCT therapeutic efficacy to treat oral cancer in this experimental model employing boron compounds approved for their use in humans (Kreimann et al , ; Trivillin et al , ) and novel boron compounds (Heber et al , ). Despite therapeutic success, the inhibition of tumor development from field‐cancerized tissue remained an unresolved challenge (Heber et al , ).…”