Inorganic Metal Hydroxide Nanoparticles for Targeted Cellular Uptake Through Clathrin‐Mediated Endocytosis

Abstract Layered double hydroxides (LDHs) are biocompatible materials which can be used as drug‐delivery nanovehicles. In order to define the optimum size of LDH nanoparticles for efficient cellular uptake and drug‐delivery pathway, we prepared different sized LDH nanoparticles with narrow size distribution by modulating the crystal growth rate, and labelled each LDH particle with a fluorophore using a silane coupling reaction. The cellular uptake rate of LDHs was found to be highly dependent on particle size (50>200≥100>350 nm), whose range of 50 to 200 nm was selectively internalized into cells through clathrin‐mediated endocytosis with enhanced permeability and retention. Our study clearly shows that not only the particle size plays an important role in the endocytic pathway and processing, but also the size control of LDH nanoparticles results in their targeted uptake to site‐specific clathrin‐mediated endocytosis. This result provides a new perspective for the design of LDH nanoparticles with maximum ability towards targeted drug delivery.