Cancer is among the leading causes of death worldwide. According to International Agency for Research on Cancer, cancer burden rises to 18.1 million new cases and 9.6 million deaths in 2018. Most of the FDA approved anticancer drugs are purely organic molecules. The successful introduction of cisplatin as an anticancer drug in the early 1980’s opened the possibility to investigate the potential applications of organometallic complexes in medicine. Boron and carbon are the elements that have the property to build molecules of unlimited size by covalent self-bonding. Largely, the white solid twelve-vertex C2B10H12 carboranes, rank among the most chemical and biological stable molecular compounds known, which display many particular characteristics that do not find a parallel in their organic counterparts. Current chemotherapy cancer treatments not only kill both cancer and healthy cells but also frequently produces drug resistance in human patients that makes treatment failure. In order to overcome this situation, more effective and selective treatments are necessary. Boron Neutron Capture Therapy (BNCT), based on the large capture neutrons surface of 10B atoms, is a promising binary therapy for the treatment of cancer, because malignant cells can be selectively targeted and destroyed.
Following our research based on the development of a new hybrid compounds’ families that offering the possibility of dual action (chemiotherapy + radiotherapy) may result into significant clinical benefits. The reported bifunctional nanoparticles (1-MNPs) combine magnetic core and icosahedral boron-clusters to develop new bimodal cancer treatment (thermoterapy + BNCT) with the aim to obtain the best therapeutic effect using the lowest doses and therefore avoiding unwanted organism toxicity and side effects suffered by the patient. The cellular uptake and toxicity profile of 1-MNPs from culture media by human brain endothelial cells (hCMEC/D3) and glioblastoma multiform A172 cell line were demonstrated as well as colloidal stability studies in different culture media and temperatures. Importantly, thermal neutrons irradiation in BNCT reduced by 2.5 the number of cultured glioblastoma cells after 1-MNP treatment, and the systemic administration of 1-MNPs in mice was well tolerated with no major signs of toxicity.
Combining magnetic nanoparticles and icosahedral boron clusters in biocompatible inorganic nanohybrids for cancer therapy
Oleshkevich, Elena; Morancho, Anna; Saha, Arpita; Galenkamp, Koen M. O.; Grayston, Alba; Crich, Simonetta Geninatti; Alberti, Diego; Protti, Nicoletta; Comella, Joan X.; Teixidor, Francesc; Rosell, Anna; Vinas, Clara
Nanomedicine: Nanotechnology, Biology, and Medicine 20 (2019) 101986
Figure: Schematic representation of the bifunctional magnetic nanoparticles (1-MNPs) and a TEM image of a A172 glioblastoma cell showing the presence of 1-MNPs into the cytoplasm with a larger load.