The Journey and Modes of Action of Therapeutic Nanomaterials in Cells

Over past decades, a wide range of nanomaterials have been synthesized and exploited to augment the efficacy and biocompatibility of disease theranostics and nanomedicine. The unique physicochemical properties of nanomaterials, such as high specific surface area, tunable size and shape, and versatile surface chemistry, enable the controlled modulation of nanomaterial-biosystem interactions and, consequently, more precise interventions, particularly at the cellular level. The selective modulation of nanomaterial-cell interactions can be leveraged to regulate cellular internalization, intracellular trafficking and localization, and cellular clearance of nanomaterials to enhance the disease therapeutic efficacy and minimize potential cytotoxicity. Herein, we provide an overview of our recent understanding of the journey and modes of action of therapeutic nanomaterials in cells. Specifically, we highlight the various pathways of cellular internalization, trafficking, and excretion of these nanomaterials. The different modes of action of therapeutic nanomaterials, especially controlled release and delivery, photothermal and photodynamic effects, and immunomodulation, are also discussed. We conclude our review by offering some perspectives on the current challenges and potential opportunities in this field.