Pre-targeting with ultra-small nanoparticles: boron carbon dots as drug candidates for boron neutron capture therapy
Irene V. J. Feiner, Krishna R. Pulagam, Kepa B. Uribe, Rossana Passannante, Cristina Simó, Kepa Zamacola, Vanessa Gómez‐Vallejo, Natalia Herrero-Álvarez, Unai Cossío, Zuriñe Baz, María M. Caffarel, Charles H. Lawrie, Daniëlle J. Vugts, Luka Rejc, Jordi Llop
Abstract
Boron neutron capture therapy (BNCT) is a promising cancer treatment exploiting the neutron capture capacity and subsequent fission reaction of boron-10. The emergence of nanotechnology has encouraged the development of nanocarriers capable of accumulating boron atoms preferentially in tumour cells. However, a long circulation time, required for high tumour accumulation, is usually accompanied by accumulation of the nanosystem in organs such as the liver and the spleen, which may cause off-target side effects. This could be overcome by using small-sized boron carriers via a pre-targeting strategy. Here, we report the preparation, characterisation and in vivo evaluation of tetrazine-functionalised boron-rich carbon dots, which show very fast clearance and low tumour uptake after intravenous administration in a mouse HER2 (human epidermal growth factor receptor 2)-positive tumour model. Enhanced tumour accumulation was achieved when using a pretargeting approach, which was accomplished by a highly selective biorthogonal reaction at the tumour site with trans-cyclooctene-functionalised Trastuzumab.