1: Small. 2008 Feb;4(2):247-53.

Discovery of new hexagonal supramolecular nanostructures formed by
squalenoylation of an anticancer nucleoside analogue.

Couvreur P, Reddy LH, Mangenot S, Poupaert JH, Desmaële D, Lepêtre-Mouelhi S,
Pili B, Bourgaux C, Amenitsch H, Ollivon M.

Université Paris-Sud XI, Faculté de Pharmacie, UMR CNRS 8612, IFR 141, 92296
Châtenay-Malabry Cedex, France.

In this study, the dynamically folded conformation of squalene (SQ) is taken
advantage of to link this natural compound to the anticancer nucleoside analogue 
gemcitabine (gem) in order to achieve the spontaneous formation of nanoassemblies
(SQgem) in water. Cryogenic transmission electron microscopy examination reveals 
particles (104 nm) with a hexagonal or multifaceted shape that display an
internal structure made of reticular planes, each particle being surrounded by an
external shell. X-ray diffraction evidences the hexagonal molecular packing of
SQgem, resulting from the stacking of direct or inverse cylinders. The respective
volumes of the gem and SQ molecules as well as molecular modeling of SQgem
suggest the stacking of inverse hexagonal phases, in which the central aqueous
core, consisting of water and gem molecules, is surrounded by SQ moieties. These 
SQgem nanoassemblies also exhibit impressively greater anticancer activity than
gem against a solid subcutaneously grafted tumor, following intravenous
administration. To our knowledge, this is the first demonstration of hexagonal
phase organization with a SQ derivative.


PMID: 18247384 [PubMed - indexed for MEDLINE]

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