Cationic liposome-nucleic acid nanoparticle assemblies with applications in gene delivery and gene silencing.
Cationic liposomes (CLs) are synthetic carriers of nucleic acids in gene delivery and gene silencing therapeutics. The introduction will describe the structures of distinct liquid crystalline phases of CL-nucleic acid complexes, which were revealed in earlier synchrotron small-angle X-ray scattering experiments. When mixed with plasmid DNA, CLs containing lipids with distinct shapes spontaneously undergo topological transitions into self-assembled lamellar, inverse hexagonal, and hexagonal CL-DNA phases. CLs containing cubic phase lipids are observed to readily mix with short interfering RNA (siRNA) molecules creating double gyroid CL-siRNA phases for gene silencing. Custom synthesis of multivalent lipids and a range of novel polyethylene glycol (PEG)-lipids with attached targeting ligands and hydrolysable moieties have led to functionalized equilibrium nanoparticles (NPs) optimized for cell targeting, uptake or endosomal escape. Very recent experiments are described with surface-functionalized PEGylated CL-DNA NPs, including fluorescence microscopy colocalization with members of the Rab family of GTPases, which directly reveal interactions with cell membranes and NP pathways. In vitro optimization of CL-DNA and CL-siRNA NPs with relevant primary cancer cells is expected to impact nucleic acid therapeutics in vivo. This article is part of the themed issue 'Soft interfacial materials: from fundamentals to formulation'.
Department of Materials, University of California, Santa Barbara, CA 93106, USA Department of Physics, University of California, Santa Barbara, CA 93106, USA Molecular, Cellular and Developmental Biology Department, University of California, Santa Barbara, CA 93106, USA.
Ramsey N
RN
Majzoub
Department of Materials, University of California, Santa Barbara, CA 93106, USA Department of Physics, University of California, Santa Barbara, CA 93106, USA Molecular, Cellular and Developmental Biology Department, University of California, Santa Barbara, CA 93106, USA.
Kai K
http://orcid.org/0000-0002-4861-8278
KK
Ewert
Department of Materials, University of California, Santa Barbara, CA 93106, USA Department of Physics, University of California, Santa Barbara, CA 93106, USA Molecular, Cellular and Developmental Biology Department, University of California, Santa Barbara, CA 93106, USA safinya@mrl.ucsb.edu.
Cyrus R
http://orcid.org/0000-0002-3295-7128
CR
Safinya
D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000493:pharmacokinetics; D002412:Cations / Q000737:chemistry / Q000493:pharmacokinetics; D002460:Cell Line; D020868:Gene Silencing; D006801:Humans; D008081:Liposomes / Q000737:chemistry / Q000493:pharmacokinetics; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D036103:Nanotechnology; D009696:Nucleic Acids / Q000737:chemistry / Q000493:pharmacokinetics; D014162:Transfection / Q000379:methods*
D001672:Biocompatible Materials; D002412:Cations; D008081:Liposomes; D009696:Nucleic Acids
PEGylated nanoparticles; Rab GTPases; cationic liposomes; fluorescence optical imaging; gene therapy; small-angle X-ray scattering