Cellular journey of nanomaterials: Theories, trafficking, and kinetics

Engineered nanomaterials (NMs) are increasingly fabricated in various fields involving consumer goods, waste management, and biomedical applications such as drug delivery, diagnosis, and treatment of pathological conditions. While these NMs are intentionally or unexpectedly in contact with the human body, there are growing concerns about their intracellular journey, especially considering the therapeutic or deleterious effects after they cross the cell membrane. In this review, the cellular journey of NMs including internalization, intracellular trafficking, and deposition/exocytosis is systematically discussed. This work highlights the accumulation of NMs in cells not only depends on the moment of NMs crossing the cell membrane but also at the following trafficking and exocytosis process. A deeper understanding of the cellular journey of NMs implies that an alternative strategy to fabricate specific targeting NMs is to bypass a few pathways of intracellular trafficking to achieve potent therapeutic effects with minimal toxicity. After comprehensively reviewing the cellular journey of NMs, current progress and application scenarios of kinetic models are discussed. Finally, this review focuses on the bottleneck problems and the corresponding solution technologies for studying the cellular journey of NMs. Recent progresses on the cellular journey of NMs provide new insights into the fabrication of biomedical NMs and facilitate technology development for probing the nano-cell interaction with high temporal-spatial resolution.