Increased local tumor control through nanoparticle-mediated, radiation-triggered release of nitrite, an important precursor for reactive nitrogen species.

Increased local tumor control through nanoparticle-mediated, radiation-triggered release of nitrite, an important precursor for reactive nitrogen species. Phys Med Biol. 2020 Jul 28;: Authors: Kim AS, Melemenidis S, Gustavsson AK, Abid D, Wu Y, Liu F, Hristov D, Schüler E Abstract The efficacy of dose-enhancing gold nanoparticles (AuNPs) is negatively impacted by low tumor uptake, low cell membrane penetration, limited diffusion distance, and short lifetime of radiation-induced secondary particles. To overcome these limitations, we have developed a novel AuNP system capable of radiation-triggered release of nitrite, a precursor of reactive nitrogen species (RNS), and report here on the in vivo characterization of this system. AuNPs were functionalized through PEGylation, cell-penetrating peptides (CPP; AuNP@CPP), and nitroimidazole (nIm; AuNP@nIm-CPP). Mice with subcutaneous 4T1 tumors received either AuNP@nIm-CPP or AuNP@CPP intraperitoneally. Tumor and normal tissue uptake were evaluated 24 hours post AuNP administration. A separate cohort of mice was injected and irradiated to a single-fraction dose of 18Gy in a 225 kVp small animal irradiator 24 hours post NP administration. The mice were followed for two weeks to evaluate tumor response. The mean physical and hydrodynamic size of both NP systems were 5nm and 13nm, respectively. NP nIm-loading of 1wt% was determined. Tumor accumulation of AuNP@nIm-CPP was significantly lower tha...
Source: Physics in Medicine and Biology - Category: Physics Authors: Tags: Phys Med Biol Source Type: research