Subcellular compartment targeting of layered double hydroxide nanoparticles

• Published in: Journal of controlled release Vol. 130; no. 1; pp. 86 - 94
• Main Authors: Xu, Zhi Ping, Niebert, Marcus, Porazik, Katharina, Walker, Tara L., Cooper, Helen M., Middelberg, Anton P.J., Gray, Peter P., Bartlett, Perry F., Lu, Gao Qing (Max)
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 25.08.2008; Elsevier
• Subjects: Aluminum Hydroxide - chemistry; Animals; Biological and medical sciences; Cell Survival - drug effects; Cellular uptake; CHO Cells; Clathrin - metabolism; Clathrin-mediated endocytosis; Cricetinae; Cricetulus; Drug Carriers - adverse effects; Drug Carriers - chemistry; Drug-Related Side Effects and Adverse Reactions; Endocytosis - drug effects; Fluorescein-5-isothiocyanate - chemistry; Gene Transfer Techniques; General pharmacology; Hydroxides - adverse effects; Hydroxides - chemistry; Layered double hydroxides; Magnesium Hydroxide - chemistry; Medical sciences; Mice; Microscopy, Confocal; Morphology; Nanoparticles - adverse effects; Nanoparticles - chemistry; NIH 3T3 Cells; Particle Size; Pharmaceutical Preparations - administration & dosage; Pharmaceutical Preparations - chemistry; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Subcellular compartment targeting; Subcellular Fractions - metabolism; Cellular uptake; Clathrin-mediated endocytosis; Subcellular compartment targeting; Morphology; Layered double hydroxides; Microparticle; Target; Pharmaceutical technology; Targeting; Nanoparticle; Layered double hydroxides;Cellular uptake;Clathrin-mediated endocytosis;Morphology;Subcellular compartment targeting
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2008.05.021

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 Mg 2Al–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 LDH FTIC nanoparticles are observed to immediately transfect into different mammalian cell lines. We found that internalized LDH FITC nanorods are quickly translocated into the nucleus while internalized LDH FITC 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 LDH FITC nanoparticles is suggested to occur through the deacidification of LDH nanoparticles. Since quick nuclear targeting of LDH FITC 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.