Intracellular trafficking pathway of layered double hydroxide nanoparticles in human cells: Size-dependent cellular delivery

Layered double hydroxide (LDH) nanoparticles are promising candidates as delivery carriers, since they have low toxicity and can intercalate anionic drugs or genes in the interlayer spaces of two dimensional lattices. However, little information is available about their intracellular fate and trafficking pathway in human cells, which is important to improve delivery efficiency and predict toxicity potential. From the immunofluorescence and confocal microscopic studies to evaluate intracellular colocalization of fluorescein isothiocyanate-labeled nanoparticles (50 and 100 nm) with specific compartments, we found that the cellular uptake reached a maximum level at 0.5 h and gradually decreased over time. The present nanoparticles were highly colocalized with early endosomes within the first 0.5 h and largely found in an exocytic organelle, the Golgi apparatus over a period of 1–24 h. Most of 100 nm could escape a typical endo-lysosomal degradation, while 50 nm followed an endosome–lysosome pathway as well as exocytosis one with the same degree. A model for the intracellular trafficking of LDH nanoparticles depending on particle size is proposed on the basis of quantitative analysis data.