TY - JOUR
T1 - How cationic lipids transfer nucleic acids into cells and across cellular membranes
T2 - Recent advances
AU - Rehman, Zia Ur
AU - Zuhorn, Inge S.
AU - Hoekstra, Dick
PY - 2013/2/28
Y1 - 2013/2/28
N2 - Cationic lipid- and polymer-based nanodevices are considered appropriate alternatives for virus-based particles for delivery of nucleic acids, including genes and siRNA, into eukaryotic cells. Because of colloidal stability concerns and toxicity issues the potential in vivo application of these so-called non-viral systems, in particular cationic lipids, was met with considerable skepticism. However, in recent years, the development of novel ionizable cationic lipid formulations in conjunction with sophisticated procedures to carefully control the size of the nanoparticles has rapidly advanced options for a successful therapeutic application. Thus it would appear that cationic lipids have taken a prominent step ahead in their potential use as nanocarriers for siRNA delivery in gene silencing of target genes in a variety of diseases. Verification and improvement of delivery efficiency as well as screening of targeting ligands justify further work in revealing underlying mechanisms that are instrumental in efficient crossing of cellular barriers by cationic lipid-based nanocarriers. In this regard, triggering entry into specific pathways or modulating trafficking along such pathways, either by targeting of nanoparticles or by affecting specific cellular signaling pathways, may represent promising tools. Such options may involve, for example, facilitating nanoparticle transport across endothelial cells by transcytotic mechanisms, or improving delivery efficiency by affecting nanoparticle trafficking that avoids lysosomal delivery. Here, recent progress in the field of lipid-based nanocarriers is discussed, with a focus on mechanisms underlying their interactions with cells in vitro. Where appropriate, we will include mechanisms for polymer-based systems in our discussion. (C) 2012 Elsevier B.V. All rights reserved.
AB - Cationic lipid- and polymer-based nanodevices are considered appropriate alternatives for virus-based particles for delivery of nucleic acids, including genes and siRNA, into eukaryotic cells. Because of colloidal stability concerns and toxicity issues the potential in vivo application of these so-called non-viral systems, in particular cationic lipids, was met with considerable skepticism. However, in recent years, the development of novel ionizable cationic lipid formulations in conjunction with sophisticated procedures to carefully control the size of the nanoparticles has rapidly advanced options for a successful therapeutic application. Thus it would appear that cationic lipids have taken a prominent step ahead in their potential use as nanocarriers for siRNA delivery in gene silencing of target genes in a variety of diseases. Verification and improvement of delivery efficiency as well as screening of targeting ligands justify further work in revealing underlying mechanisms that are instrumental in efficient crossing of cellular barriers by cationic lipid-based nanocarriers. In this regard, triggering entry into specific pathways or modulating trafficking along such pathways, either by targeting of nanoparticles or by affecting specific cellular signaling pathways, may represent promising tools. Such options may involve, for example, facilitating nanoparticle transport across endothelial cells by transcytotic mechanisms, or improving delivery efficiency by affecting nanoparticle trafficking that avoids lysosomal delivery. Here, recent progress in the field of lipid-based nanocarriers is discussed, with a focus on mechanisms underlying their interactions with cells in vitro. Where appropriate, we will include mechanisms for polymer-based systems in our discussion. (C) 2012 Elsevier B.V. All rights reserved.
KW - Nanocarriers
KW - Cationic lipids
KW - Lipoplex
KW - Polyplex
KW - Intracellular trafficking
KW - Mechanism
KW - CAVEOLAE-MEDIATED ENDOCYTOSIS
KW - NONVIRAL GENE DELIVERY
KW - LIPOSOME-DNA COMPLEXES
KW - HEPARAN-SULFATE PROTEOGLYCANS
KW - IN-VITRO
KW - INTRACELLULAR DELIVERY
KW - GEMINI SURFACTANTS
KW - ENDOSOMAL ESCAPE
KW - PHASE-BEHAVIOR
KW - NANOPARTICLE UPTAKE
U2 - 10.1016/j.jconrel.2012.12.014
DO - 10.1016/j.jconrel.2012.12.014
M3 - Review article
SN - 0168-3659
VL - 166
SP - 46
EP - 56
JO - Journal of Controlled Release
JF - Journal of Controlled Release
IS - 1
ER -