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

一种新型 pH 敏感诊疗 PLGA 纳米粒子,用于间皮瘤治疗中的硼中子俘获疗法

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作者:Jacopo Sforzi, Alberto Lanfranco, Rachele Stefania, Diego Alberti, Valeria Bitonto, Stefano Parisotto, Polyssena Renzi, Nicoletta Protti, Saverio 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.

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