br Key words m Carboranyl Phosphinate Iron oxide nanoparticles Boron
Key words: m-Carboranyl; Phosphinate; Iron oxide nanoparticles; Boron neutron capture therapy; Nanomedicine
The synthesis of magnetic nanoparticles (MNPs) has been intensively developed for many technological1 and medical applications.2,3 Typical MNPs obtained by bottom up synthesis consist of a magnetic core and an organic or inorganic shell that provides a barrier between the core and its environment
Conflicts of interest: the authors declare no conflicts of interest. Correspondence to: A. Rosell, Vall d'Hebron Research institute, Passeig Vall d'Hebron 119-129, 08035, Barcelona, Spain.
Correspondence to: C. Viñas, Institut de Ciència de Materials de Barcelona (ICMAB-CSIC), Campus U.A.B., 08193 Bellaterra, Spain.
E-mail addresses: [email protected] (A. Rosell), [email protected] (C. Viñas).
dispersing them in water at a range of different pH, among other tasks. While MNPs' physical properties are determined by their inorganic magnetic core, their surface properties also play an important role, especially in effective interfacing (e.g., ensuring biocompatibility and specific site) with biological systems. Superparamagnetic iron oxide nanoparticles (SPIONs or MNPs) have been extensively investigated for numerous in vivo and in vitro applications, such as magnetic resonance imaging (MRI) E-64-c enhancement,4 tissue repair, detoxifica-tion of biological fluids, hyperthermia, drug delivery, immuno-assays and cell separation techniques.2
All these biomedical applications require that MNPs have high magnetization values, a size smaller than 100 nm, and a narrow particle size distribution. These applications also require a demanding surface coating of the MNPs, which has to be nontoxic
and biocompatible.5 Such MNPs have been bound to drugs, proteins, enzymes, antibodies, or nucleotides and can be directed to an organ, tissue, or tumor using an external magnetic field.6,7 However, only one example of o-carborane cages attached to MNPs through a long linker for cancer treatment can be found in the literature.8 Among different surface coating o-carborane cages, carboranylphosphinates,9 have many advantages due to their good affinity towards MNPs, their highly biocompatible tridimensional structure and their high boron content, which can be exploited for Boron Neutron Capture Therapy(BNCT) which is based on the nuclear capture and fission reactions that occur when the stable isotope 10B is irradiated with epithermal neutron beam radiation in clinical use, which become thermalized as they penetrate tissue.10
The most studied carborane is 1,2-dicarba-closo-dodecabor-ane, 1,2-closo-C2B10H12, and its isomers (1,7 and 1,12-) that can be viewed as 3D aromatic systems11 whose volume approximates that of one displayed by a benzene molecule rotating on one of its twofold axes.12 These carboranes exhibit an unusual combination of properties such as low nucleophi-licity, chemical inertness, thermal stability,13,14 as well as stability and low toxicity in biological systems.15–21 The rigid
geometry and the relative easy functionalization at the carbon vertexes of the carborane cluster13,22,23 allow the preparation of
a wide number of compounds potentially useful as precursors of more complex materials.24–29 Furthermore, the use of carbor- anes in supramolecular chemistry is a topic, which raises great interest for their particular properties 12,30–34 that may induce an unexpected behavior in the supramolecular structures in which they are inserted. Our vision of the carboranyl substituent, however, is that it is unique as a ligand because it is a hollow rigid sphere appended to a metal coordinating site. This, along with its hydrophobicity and electron withdrawing properties through the carbon cluster, Cc,35–37 suggests the possibility of inducing distinct geometrical behavior in boron rich macromol-ecules or particles of significance for Boron Neutron Capture Therapy (BNCT),38–44 an alternative radiotherapy used for aggressive and infiltrating types of cancer that can not be treated
with surgery or standard radio or chemotherapy, and by drug delivery.38,45
The theoretical advantage of BNCT is that it can selectively destroy tumor cells infiltrating normal tissue with the requirement that sufficient amounts of 10B and thermal neutrons are properly delivered to the site of the tumor.38–45 Clinical interest in BNCT has focused primarily on high grade gliomas and on recurrent tumors of the head and neck region who have failed conventional therapy. BNCT integrates the focusing approach of chemotherapy and the gross anatomical localization advantage of traditional radiotherapy, offering the ability to deposit an immense dose-gradient between the tumor cells and normal cells.46 For this, new and better boron delivery agents targeting cancer cells are needed for the clinical use.