title: 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 Mg(2)Al-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.
authors.affiliation: ARC Centre of Excellence for Functional Nanomaterials, School of Engineering, The University of Queensland, Brisbane, QLD 4072, Australia. gordonxu@uq.edu.au
authors.forename: Zhi Ping
authors.initials: ZP
authors.lastname: Xu
authors.forename: Marcus
authors.initials: M
authors.lastname: Niebert
authors.forename: Katharina
authors.initials: K
authors.lastname: Porazik
authors.forename: Tara L
authors.initials: TL
authors.lastname: Walker
authors.forename: Helen M
authors.initials: HM
authors.lastname: Cooper
authors.forename: Anton P J
authors.initials: AP
authors.lastname: Middelberg
authors.forename: Peter P
authors.initials: PP
authors.lastname: Gray
authors.forename: Perry F
authors.initials: PF
authors.lastname: Bartlett
authors.forename: Gao Qing Max
authors.initials: GQ
authors.lastname: Lu
mesh_terms: D000536:Aluminum Hydroxide / Q000737:chemistry; D000818:Animals; D016466:CHO Cells; D002470:Cell Survival / Q000187:drug effects; D002966:Clathrin / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D004337:Drug Carriers / Q000009:adverse effects / Q000737:chemistry*; D064420:Drug-Related Side Effects and Adverse Reactions; D004705:Endocytosis / Q000187:drug effects; D016650:Fluorescein-5-isothiocyanate / Q000737:chemistry; D018014:Gene Transfer Techniques; D006878:Hydroxides / Q000009:adverse effects / Q000737:chemistry*; D008276:Magnesium Hydroxide / Q000737:chemistry; D051379:Mice; D018613:Microscopy, Confocal; D041681:NIH 3T3 Cells; D053758:Nanoparticles / Q000009:adverse effects / Q000737:chemistry*; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000737:chemistry; D013347:Subcellular Fractions / Q000378:metabolism
chemical_list: D002966:Clathrin; D004337:Drug Carriers; D006878:Hydroxides; D004364:Pharmaceutical Preparations; D000536:Aluminum Hydroxide; D016650:Fluorescein-5-isothiocyanate; D008276:Magnesium Hydroxide