Subcellular compartment targeting of layered double hydroxide nanoparticles

Abstract

Current investigations show that layered double hydroxide (LDH) nanoparticles have high potential as effective non-viral agents for cellular drug delivery due to their low cytotoxicity, good biocompatibility, high drug loading, control of particle size and shape, targeted delivery and drug release control. Two types of Mg2Al-LDH nanoparticles with fluorescein isothiocyanate (FITC) were controllably prepared. One is morphologically featured as typical hexagonal sheets (50-150 nm laterally wide and 10-20 nm thick), while the other as typical rods (30-60 nm wide and 100-200 nm long). These LDHFTIC nanoparticles are observed to immediately transfect into different mammalian cell lines. We found that internalized LDHFITC nanorods are quickly translocated into the nucleus while internalized LDHFITC nanosheets are retained in the cytoplasm. Inhibition experiments show that the cellular uptake is a clathrin-mediated time- and concentration-dependent endocytosis. Endosomal escape of LDHFITC nanoparticles is suggested to occur through the deacidification of LDH nanoparticles. Since quick nuclear targeting of LDHFITC nanorods requires an active process, and although the exact mechanism is yet to be fully understood, it probably involves an active transport via microtubule-mediated trafficking processes. Targeted addressing of two major subcellular compartments by simply controlling the particle morphology/size could find a number of applications in cellular biomedicine. © 2008 Elsevier B.V. All rights reserved.