Quantifying nanodiamonds biodistribution in whole cells with correlative iono-nanoscopy.
Zhaohong MiCe-Belle ChenHong Qi TanYanxin DouChengyuan YangShuvan Prashant TuragaMinqin RenSaumitra K VajandarGin Hao YuenThomas OsipowiczFrank WattAndrew A BettiolPublished in: Nature communications (2021)
Correlative imaging and quantification of intracellular nanoparticles with the underlying ultrastructure is crucial for understanding cell-nanoparticle interactions in biological research. However, correlative nanoscale imaging of whole cells still remains a daunting challenge. Here, we report a straightforward nanoscopic approach for whole-cell correlative imaging, by simultaneous ionoluminescence and ultrastructure mapping implemented with a highly focused beam of alpha particles. We demonstrate that fluorescent nanodiamonds exhibit fast, ultrabright and stable emission upon excitation by alpha particles. Thus, by using fluorescent nanodiamonds as imaging probes, our approach enables quantification and correlative localization of single nanodiamonds within a whole cell at sub-30 nm resolution. As an application example, we show that our approach, together with Monte Carlo simulations and radiobiological experiments, can be employed to provide unique insights into the mechanisms of nanodiamond radiosensitization at the single whole-cell level. These findings may benefit clinical studies of radio-enhancement effects by nanoparticles in charged-particle cancer therapy.
Keyphrases
- high resolution
- single cell
- electron microscopy
- cell therapy
- induced apoptosis
- monte carlo
- cancer therapy
- stem cells
- living cells
- fluorescence imaging
- quantum dots
- photodynamic therapy
- oxidative stress
- single molecule
- computed tomography
- cell proliferation
- small molecule
- endoplasmic reticulum stress
- cell death
- high density
- pet ct
- reactive oxygen species