Bnct and Nanoparticles: A Long Way to a Routine Clinical Method

Abstract

is influenced by several parameters, including: the intrinsic properties of the nanomaterial (size, porosity, surface polarity), the characteristics of the medium (viscosity, pH, ionic strength, ionic composi tion, presence of molecules and/or macromolecules), and nanoparticle concentration. The addition of various molecules can partially stabilize some types of nanoparticles in suspension, but often these additives are not compatible for medical use, because toxic (e.g. alcohols, surfactants) or anyway contraindicated for intravenous injection (2,3). We have recently had the chance to read the editorial Boron Neutron Capture Therapy of cancer as a part of modern nanomedicine (1), by Alexander V. Safronov, in which the potential of nanomaterials as boron-carriers for the treatment of many types of tumors by BNCT is discusses. The author argues that Most of the modern papers on BNCT report 'potential' BNCT agents (…) and don't even include cell studies, and some cases the abbreviation BNCT may become a 'golden ticket' for authors who just want to public their current study without intent to continue. We agree with the first assertion, which is unequivocally verifiable by reading the recent literature about BNCT, but not with the second, that is somewhat speculative. The study for a new drug is complex and may last ten years or more. It includes the preparation of the molecule in a pure form, the experimentation on cell lines, the animal testing, and the three phases of clinical trials on humans. In the case in which in vitro results already point to a possible cytotoxicity, additional in vivo tests on animals become inopportune on the basis of ethical principles that have been even reinforced by novel laws promulgated in some countries, such as the new European regulation (2010/63/UE), that strongly restrict inessential in vivo experiments. Therefore, a scientific work can be interrupted at an early stage and, unfortunately, the obtained data remain generally unpublished, staying hidden to the rest of the world. In a field such as nanotechnology, when little differences in size, shape and chemical-physical properties of nanoparticles induce great alterations in the interaction with biological systems, the failures and the frustrating difficulties in the interpretation of the results are widespread. A dramatic obstacle that is encountered in the application of nanomaterials for biological purposes (especially for BNCT, in which the compound must be administered as a homogeneous suspension by intravenous infusion), is their strong tendency to aggregate/agglomerate, in aqueous solvents, into large particles of micrometric size, by reason of their thermodynamic properties. These micrometric particles, besides having an elevated sedimentation rate, induce several adverse reactions to blood components (e.g. thrombi, inflammation, and hemolysis) and, most importantly, will never be internalized by target cells. The stability of nanoparticle suspensions