Dynamic nano-assemblies based on two-dimensional inorganic nanoparticles: Construction and preclinical demonstration

Abstract Dynamic drug delivery systems (DDSs) have the ability of transforming their morphology and functionality in response to the biological microenvironments at the disease site and/or external stimuli, show spatio-temporal controllable drug delivery, and enhance the treatment efficacy. Due to the large surface area and modification flexibility, two-dimensional (2D) inorganic nanomaterials are being increasingly exploited for developing intelligent DDSs for biomedical applications. In this review, we summarize the engineering methodologies used to construct transformable 2D DDSs, including changing compositions, creating defects, and surface dot-coating with polymers, biomolecules, or nanodots. Then we present and discuss dynamic inorganic 2D DDSs whose transformation is driven by the diseased characteristics, such as pH gradient, redox, hypoxia, and enzyme in the tumor microenvironment as well as the external stimuli including light, magnetism, and ultrasound. Finally, the limitations and challenges of current transformable inorganic DDSs for clinical translation and their safety assessment for clinical applications are discussed.