Therapeutic efficacy of boron neutron capture therapy mediated by boron-rich liposomes for oral cancer in the hamster cheek pouch model
The application of boron neutron capture therapy (BNCT) mediated by liposomes containing ¹⁰B-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...
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Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2014-11, Vol.111 (45), p.16077-16081 |
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Zusammenfassung: | The application of boron neutron capture therapy (BNCT) mediated by liposomes containing ¹⁰B-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 ₂B ₉H ₁₁] (MAC) in the bilayer membrane while encapsulating the hydrophilic species Na ₃[ ae -B ₂₀H ₁₇NH 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%.
Significance Boron neutron capture therapy (BNCT) for cancer is based on the selective uptake of ¹⁰B target compounds by tumor cells followed by neutron irradiation. The capture reaction between ¹⁰B atoms and neutrons gives rise to short-range particles, which are highly effective in producing cell damage. Thus, BNCT is designed to damage tumor cells and preserve healthy cells. The boron carrier used is pivotal to the success of BNCT. The present study describes the therapeutic success of BNCT mediated by MAC-TAC liposomes, K[ nido -7-CH ₃(CH ₂) ₁₅-7,8-C ₂B ₉H ₁₁] (MAC) in the bilayer membrane and encapsulating the hydrophilic species Na ₃[ ae -B ₂₀H ₁₇NH ₃] (TAC) in the aqueous core, using the hamster cheek pouch oral cancer model. A sustained tumor response of 70–88% was associated with only mild mucositis in dose-limiting precancerous tissue. |
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ISSN: | 0027-8424 1091-6490 |
DOI: | 10.1073/pnas.1410865111 |