Abstract
Extra-large nanochannel formation in the internal structure of cationic cubosome nanoparticles results from the interplay between charge repulsion and steric stabilization of the lipid membrane interfaces and is evidenced by cryogenic transmission electron microscopy (Cryo-TEM) and synchrotron radiation small-angle X-ray scattering (SAXS). The swollen cubic symmetry of the lipid nanoparticles emerges through a shaping transition of onion bilayer vesicle intermediates containing a fusogenic nonlamellar lipid. Cationic amphiphile cubosome particles, thanks to the advantages of their liquid crystalline soft porous nanoarchitecture and capability for multi-drug nanoencapsulation, appear to be of interest for the design of mitochondrial targeting devices in anti-cancer therapies and as siRNA nanocarriers for gene silencing.
Highlights
Bicontinuous lipid cubic phases with large water channels have been evidenced by small angle X-ray scattering (SAXS).8c–g Their inner liquid crystalline (LC) architecture involves organized 3D lipid membrane labyrinths that separate intertwined networks of water-swollen channel compartments.[10,11] Large water nanochannels represent a protein-friendly environment for either water-soluble or membrane anchored proteins.2a,c,3b,4,6b Almsherqi et al have discovered biomembranes of cubic symmetries with considerably swollen nanochannels in samples of biological origin.14a This fact has suggested that aqueous channel formation on the mesoscale has important biological significance in health and disease states
We investigate the mechanism of formation of water-swollen channels of cubic symmetry within individual PEGylated cubosome nanoparticles
It is noteworthy that the immediate recognition of extra-large channel cubosomes by Cryo-TEM imaging might not be straightforward in the absence of structural SAXS data
Summary
Bicontinuous lipid cubic phases with large water channels (channel size bigger than 6 nm) have been evidenced by small angle X-ray scattering (SAXS).8c–g Their inner LC architecture involves organized 3D lipid membrane labyrinths that separate intertwined networks of water-swollen channel compartments.[10,11] Large water nanochannels represent a protein-friendly environment for either water-soluble or membrane anchored proteins.2a,c,3b,4,6b Almsherqi et al have discovered biomembranes of cubic symmetries with considerably swollen nanochannels (cubic lattice size of up to 500 nm) in samples of biological origin.14a This fact has suggested that aqueous channel formation on the mesoscale has important biological significance in health and disease states. The first one consists of ‘‘top-down’’ fragmentation of bulk mesophases of lyotropic amphiphiles,[3,9] while the second one is based on ‘‘bottom-up’’ assembly of vesicular membranes.2d,6c,8a A question, which remains open in the context of the ‘‘top-down’’ approach, is whether the Pluronic polymer shell (providing long circulation of the cubosome nanoparticles)9a might ensure or hamper the diffusion of biomacromolecules in/out the nanochannelled carriers. This concern should be minor upon utilization of PEGylated lipids for cubic nanoparticle dispersion.2d,3d,6e. This fundamental problem requires elucidation from a structural view point
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