- Email: [email protected]
Cover story
Journal of Controlled Release 130 (2008) 1
Contents lists available at ScienceDirect
Journal of Controlled Release j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / j c o n r e l
Cover story
Over the past decade non-viral gene and drug delivery have been and continue to be major topics of scientific interest, with many interdisciplinary research teams developing novel transfection agents (e.g., polymeric carriers, liposomes, inorganic carriers, and many more) and delivery methods (e.g., electroporation, microinjection,…) for both in vitro and in vivo applications. However, while many transfection agents are able to efficiently deliver nucleic acids and/or drugs, they mainly do so in a random manner. In order to address specific organs in vivo or target certain intra-cellular organelles in vitro, many researchers attempt to use antibody coupling or similar techniques. While this not only increases the cost, it also introduces additional complications, e.g., non-desirable inflammatory responses in vivo and more often than not results in a loss of efficiency. Layered double hydroxide (LDH) nanoparticles have high potential as effective non-viral agents for cellular drug and gene delivery due to their low cytotoxicity, good biocompatibility, and many other desirable properties. The work published in this issue, [1] describes how these nanoparticles can be prepared exhibiting different morphologies—rod-like and hexagonal—and their influences on cellular localization. It is found that rod-like LDH nanoparticles are concentrated within the nucleus of mammalian cells and their hexagonal counterparts mainly localize in the perinuclear cytoplasm. This is the first time that different intra-cellular compartments have been targeted by a simple change in morphology of the carrier without the need for functionalization of either the carrier or the payload with targeting molecules. The cellular uptake and release
0168-3659/$ – see front matter © 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.jconrel.2008.07.003
mechanisms of particles of both morphologies were further elucidated using uptake inhibiting drugs and dominant/negative mutants of the cell lines used. It is found that the uptake of these particles is mainly facilitated by clathrin-mediated, time- and concentration-dependent endocytosis, with the nuclear translocation of the rod-like nanoparticles probably being the result of a microtubule-mediated trafficking process. It is highly possible that targeted delivery into two major subcellular compartments by simply controlling the particle morphology/size will find numerous applications in cellular biomedicine. Reference [1] Z.P. Xu, et al., Subcellular compartment targeting of layered double hydroxide nanoparticles, Journal of Controlled Release 130 (2008) 86–94.
Zhi Ping Xu Gao Qing (Max) Lu ARC Centre of Excellence for Functional Nanomaterials, School of Engineering, The University of Queensland, Brisbane, QLD 4072, Australia Tel.: +61 617 33463828; fax: +61 617 33463973. E-mail addresses: [email protected], [email protected].
Contents lists available at ScienceDirect
Journal of Controlled Release j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / j c o n r e l
Cover story
Over the past decade non-viral gene and drug delivery have been and continue to be major topics of scientific interest, with many interdisciplinary research teams developing novel transfection agents (e.g., polymeric carriers, liposomes, inorganic carriers, and many more) and delivery methods (e.g., electroporation, microinjection,…) for both in vitro and in vivo applications. However, while many transfection agents are able to efficiently deliver nucleic acids and/or drugs, they mainly do so in a random manner. In order to address specific organs in vivo or target certain intra-cellular organelles in vitro, many researchers attempt to use antibody coupling or similar techniques. While this not only increases the cost, it also introduces additional complications, e.g., non-desirable inflammatory responses in vivo and more often than not results in a loss of efficiency. Layered double hydroxide (LDH) nanoparticles have high potential as effective non-viral agents for cellular drug and gene delivery due to their low cytotoxicity, good biocompatibility, and many other desirable properties. The work published in this issue, [1] describes how these nanoparticles can be prepared exhibiting different morphologies—rod-like and hexagonal—and their influences on cellular localization. It is found that rod-like LDH nanoparticles are concentrated within the nucleus of mammalian cells and their hexagonal counterparts mainly localize in the perinuclear cytoplasm. This is the first time that different intra-cellular compartments have been targeted by a simple change in morphology of the carrier without the need for functionalization of either the carrier or the payload with targeting molecules. The cellular uptake and release
0168-3659/$ – see front matter © 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.jconrel.2008.07.003
mechanisms of particles of both morphologies were further elucidated using uptake inhibiting drugs and dominant/negative mutants of the cell lines used. It is found that the uptake of these particles is mainly facilitated by clathrin-mediated, time- and concentration-dependent endocytosis, with the nuclear translocation of the rod-like nanoparticles probably being the result of a microtubule-mediated trafficking process. It is highly possible that targeted delivery into two major subcellular compartments by simply controlling the particle morphology/size will find numerous applications in cellular biomedicine. Reference [1] Z.P. Xu, et al., Subcellular compartment targeting of layered double hydroxide nanoparticles, Journal of Controlled Release 130 (2008) 86–94.
Zhi Ping Xu Gao Qing (Max) Lu ARC Centre of Excellence for Functional Nanomaterials, School of Engineering, The University of Queensland, Brisbane, QLD 4072, Australia Tel.: +61 617 33463828; fax: +61 617 33463973. E-mail addresses: [email protected], [email protected].