Hybrid manganese dioxide nanoparticles potentiate radiation therapy by modulating tumor hypoxia
Menée à l'aide de xénogreffes de cancer mammaire sur des modèles murins, cette étude montre que des nanoparticules hybrides de dioxyde de manganèse composées de matériaux biocompatibles peuvent, en réagissant avec le péroxyde d'hydrogène endogène, réduire l'hypoxie du micro-environnement tumoral et augmenter ainsi l'efficacité d'une radiothérapie
Hypoxia in the tumor microenvironment (TME) mediates resistance to radiotherapy (RT) and contributes to poor prognosis in patients receiving RT. Here we report the design of clinically suitable formulations of hybrid manganese dioxide (MnO2) nanoparticles (MDNP) using biocompatible materials to re-oxygenate the TME by reacting with endogenous H2O2. MDNP containing hydrophilic terpolymer-protein-MnO2 or hydrophobic polymer-lipid-MnO2 provided different oxygen generation rates in the TME relevant to different clinical settings. In highly hypoxic murine or human xenograft breast tumor models, we found that administering either MDNP formulation before RT modulated tumor hypoxia and increased RT efficacy, acting to reduce tumor growth, VEGF expression and vascular density. MDNP treatment also increased apoptosis and DNA double strand breaks (DSB), increasing median host survival 3 to 5-fold. Notably, in the murine model ~40% of tumor-bearing mice were tumor-free after a single treatment with MDNP plus RT at a 2.5-fold lower dose than required to achieve the same curative treatment without MDNP. Overall, our findings offer a preclinical proof of concept for the use of MDNP formulations as effective RT adjuvants.%U http://cancerres.aacrjournals.org/content/canres/early/2016/10/06/0008-5472.CAN-15-3475.full.pdf
Cancer Research 2016