Stable isotope labeling of nanomaterials for biosafety evaluation and drug development

Quantitative information, such as environmental migration, absorption, biodistribution, biotransformation, and elimination, is fundamental and essential for the nanosafety evaluations of nanomaterials. Due to the complexity of biological and environmental systems, it is challenging to develop quantitative approaches and tools that could characterize intrinsic behaviors of nanomaterials in the organisms. The isotopic tracers are ideal candidates to tune the physical properties of nanomaterials while preserving their chemical properties. In this review article, we summarized the stable isotope labeling methods of nanomaterials for evaluating their environmental and biological effects. The skeleton labeling protocols of carbon nanomaterials and metal/metal oxide nanoparticles were introduced. The advantages and disadvantages of stable isotope labeling were discussed in comparison with other quantitative methods for nanomaterials. The quantitative information of nanomaterials in environmental and biological systems was summarized along with the biosafety data. The benefits for drug development of nanomedicine were analyzed based on the targeting effects, persistent accumulation, and safety. Finally, the challenges and future perspectives of stable isotope labeling in nanoscience and nanotechnology were discussed.