A novel pH sensitive theranostic PLGA nanoparticle for boron neutron capture therapy in mesothelioma treatment

• Published in: Scientific reports Vol. 13; no. 1; pp. 620 - 9
• Main Authors: Sforzi, Jacopo, Lanfranco, Alberto, Stefania, Rachele, Alberti, Diego, Bitonto, Valeria, Parisotto, Stefano, Renzi, Polyssena, Protti, Nicoletta, Altieri, Saverio, Deagostino, Annamaria, Geninatti Crich, Simonetta
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 12-01-2023; Nature Publishing Group; Nature Portfolio
• Subjects: 631/154; 631/67; 639/638; 692/4017; Biomarkers; Boron; Boron Neutron Capture Therapy - methods; Brain cancer; Cancer therapies; Clinical trials; Drug dosages; Glycolic acid; Glycols; Histidine; Humanities and Social Sciences; Humans; Hydrogen-Ion Concentration; Imidazole; Irradiation; Magnetic resonance imaging; Medical prognosis; Melanoma; Mesothelioma; Mesothelioma - diagnostic imaging; Mesothelioma - radiotherapy; Mesothelioma, Malignant; multidisciplinary; Nanoparticles; Neutrons; Peptides; pH effects; Polyethylene glycol; Polylactide-co-glycolide; Polymers; Precision Medicine; Science; Science (multidisciplinary); Skin cancer; Tumors
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-023-27625-0

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.