Liposomes for the delivery of boronated agents for BNCT

Boron neutron capture therapy (BNCT) is a technique used in cancer treatment which involves the selective accumulation of chemical agents containing the 10B isotope in cancer cells, followed by irradiation with thermal neutrons. The capture of a thermal neutron by a 10B nucleus initiates a nuclear reaction in which the decay of an excited 11B nucleus produces a high linear energy transfer α-particle and a lithium nucleus. The short trajectory (5–9 μm; approximately one cell diameter) of the emitted particles allows to limit damage only to 10B-containing cells, which makes this particular radiotherapy suitable for circumscribed lesion treatment. Moreover, if 10B agents can be selectively targeted to tumor cells, side effects typically associated with ionizing radiation can be avoided. However, for BNCT to be successful in the treatment of cancer, sufficiently high concentrations of 10B atoms have to be reached (≥20 μg 10B per gram of tumor tissue or 109 10B atoms per cell), as well as good retention of 10B in tumor tissue with rapid clearance from blood and normal tissues, and low systemic toxicity of the 10B delivery agent (1; 2). Our current research has focused on the development of boron-loaded drug delivery systems with the aim of maximizing the amount of 10B agents addressing the tumor tissue and of increasing the tumor/normal tissue ratio. On this purpose, pegylated liposomes were formulated, characterized, and loaded with boronophenylalanine (L-BPA), a boron agent approved for human trials. B-loaded liposomes were purified by size-exclusion chromatography and boron encapsulation efficiency was evaluated with an ICP-AES method. The future perspectives of this research will focus on the development of a targeting moiety for the selective delivery of the boron-delivery system to cancer cells.