Understanding the particokinetics of engineered nanomaterials for safe and effective therapeutic applications

Increasing numbers of engineered nanomaterials (ENMs) are being developed for therapeutic and diagnostic applications. However, the tunable and varied physicochemical properties of ENMs pose a new challenge for understanding their biological behavior, trafficking, and biodistribution. Herein the concept of "particokinetics" is introduced to address the dynamic biological behavior of ENMs at the molecular level (including gravitational sedimentation, dispersion, aggregation, and interaction with biomolecules in suspending media), cellular level (including cellular uptake, transport, biotransformation, and elimination), and whole-organism level (including absorption, distribution, metabolism, and excretion in vivo). Several mathematical modeling methods are introduced which guide a quantitative description of their biological behavior at different levels. Examples are also provided to delineate the impact of the physicochemical properties of ENMs on their particokinetics. A comprehensive understanding of the in vivo and in vitro particokinetics of ENMs will facilitate the design of tailor-made functional ENMs that act as highly effective and controllable drug-delivery systems with minimal side-effects.