Radiosensitization beyond DNA damage: Monte Carlo simulations of realistic nanomaterial biodistributions

We investigated cellular distribution of a tumor-specific gadolinium chelate in 4T1 and U87 cancer cells with the goal to generate more realistic geometries for Monte Carlo simulations of radiation interaction with nanoparticles in cells. Cells were exposed to the agent in-vitro for 30 minutes to 72 hours before being fixed and imaged using transmission electron microscopy. Initially, electron-dense areas consistent with gadolinium were observable throughout the cytoplasm. At six hours those areas were restricted to endosomes and at 24 hours or longer electron dense areas were only found in lysosomes. Lysosomes were on average larger in 4T1 cells, which were exposed to 1 mM concentration compared to U87 cells, exposed to 1 uM. Based on this information we built an extended cell model for Monte Carlo simulations that includes lysosomes with discrete nanoparticle enclaves in addition to mitochondria and the nucleus.