A novel pH sensitive theranostic PLGA nanoparticle for boron neutron capture therapy in mesothelioma treatment
Jacopo Sforzi, Alberto Lanfranco, Rachele Stefanìa, Diego Alberti, Valeria Bitonto, Stefano Parisotto, Polyssena Renzi, Nicoletta Protti, S. Altieri, Annamaria Deagostino, Simonetta Geninatti Crich
Abstract
This study aims to develop poly lactic-co-glycolic acid (PLGA) nanoparticles with an innovative imaging-guided approach based on Boron Neutron Capture Therapy for the treatment of mesothelioma. The herein-reported results demonstrate that PLGA nanoparticles incorporating oligo-histidine chains and the dual Gd/B theranostic agent AT101 can successfully be exploited to deliver a therapeutic dose of boron to mesothelioma cells, significantly higher than in healthy mesothelial cells as assessed by ICP-MS and MRI. The selective release is pH responsive taking advantage of the slightly acidic pH of the tumour extracellular environment and triggered by the protonation of imidazole groups of histidine. After irradiation with thermal neutrons, tumoral and healthy cells survival and clonogenic ability were evaluated. Obtained results appear very promising, providing patients affected by this rare disease with an improved therapeutic option, exploiting PLGA nanoparticles.