SPION@liposomes hybrid nanoarchitectures with high density SPION association Alice Floris, a Andrea Ardu, b Anna Musinu, b Giorgio Piccaluga, b Anna M. Fadda, a Chiara Sinico a and Carla Cannas * b Received 14th January 2011, Accepted 4th May 2011 DOI: 10.1039/c1sm05059a A simple, versatile and reproducible method for the preparation of hybrid inorganic–organic magnetic nanocolloids based on phospholipids and preformed magnetic nanoparticles has been proposed. Superparamagnetic hydrophilic and hydrophobic iron oxide nanoparticles (SPION) of similar size are synthesized as a first step and subsequently hybrid-lipid based assemblies containing SPION has been prepared according to the thin film hydration method (TLE) using soya phosphatidylcholine. The effects of the different nature of the nanoparticles on the features of the assemblies have been observed by TEM: the hydrophilic nanoparticles are found to be located at the external surface of the vesicle, while the hydrophobic ones are in the inner core of the vesicles. In particular, uni/oligolamellar magnetic vesicles have been achieved with hydrophilic nanoparticles and high density multilamellar magnetic vesicles have been obtained with hydrophobic magnetic nanoparticles. ‘‘Cationic’’ nanoparticles interaction with ‘‘anionic’’ phospholipids has been proposed in the case of hydrophilic nanoparticles, while an aggregation phenomenon probably due to the hydration phase during the magnetoliposome preparation and an interaction of the oleic acid coatings with lipid membrane has been suggested in the case of hydrophobic nanoparticles. Introduction Studies on nanoscale magnetic materials have captured signifi- cant scientific and industrial interest in the last ten years. In particular, the synthesis of biocompatible superparamagnetic materials has long been of interest in biomedical applications including magnetic resonance imaging for clinical diagnostics (T2/T2* contrast agent), magnetic drug targeting, hyperthermia anticancer strategy, magnetic separation, and enzyme immobi- lization. 1–10 It is well known that the efficacy of many medical applications is strongly related to the generation of narrow size distribution and well-dispersed nanoparticles in aqueous media; for this reason great effort has been devoted to the development or optimization of synthetic strategies for the fabrication of iron oxide superparamagnetic nanoparticles and their functionaliza- tion and coating. Recent advances in synthetic methods have allowed scientists to easily prepare a wide range of magnetic nanoparticles through aqueous or non-aqueous approaches. 3,11–26 Therefore, size, size distribution, shape, and crystallinity can be finely tuned by the choice of a suitable synthetic approach. In particular, in order to obtain systems easily dispersible in biological fluids, the magnetic nanoparticles have to be wrapped in biocompatible and surface-functionaliz- able materials (polymers, silica, phospholipids, etc.). 1,27–30 This step is also necessary to avoid the natural tendency of the magnetic nanoparticles to aggregate, and, in the case of hydro- phobic nanoparticles, to transform them into hydrophilic systems. Among the different coating materials, the amphiphilic phos- pholipids assembled in a bilayered structure (liposome) have gained much interest given their biocompatibility, biodegrad- ability, low toxicity, and immunogenicity. 30,31 As drug delivery systems, they may encapsulate a large amount of hydrophilic drugs in their inner core, of hydrophobic drugs inside the bilayers reducing drug toxicity, protecting them from factors that could inactivate them, and ensuring a modified release of the drug. Moreover, they are easily biofunctionalizable being the lipo- somal surface modifiable by the conjugation with specific ligands which increase the targeting efficiency to specific tissues or organs (i.e. antibodies, folates, peptides) or extend their blood- circulation time (polyethylene glycol chains). The term magnetoliposome is usually used to indicate a colloidal system in which a magnetic core, generally made up of iron oxide nanoparticles, is surrounded by a phospholipid bilayer. The classical magnetoliposomes consist of small uni- lamellar vesicles where the inner aqueous cavity is fully packed by magnetic nanoparticles thus resulting in a high iron/lipids ratio. 32,33 A second type of magnetoliposomes consists of large unilamellar vesicles in which, beside the iron oxide nanoparticles, a Universit  a di Cagliari, Dipartimento Farmaco Chimico Tecnologico, Via Ospedale 92, Cagliari, 09124, Italy b Universit  a di Cagliari, Dipartimento di Scienze Chimiche, S.S. 554 bivio per Sestu, Monserrato, Cagliari, 09042, Italy. E-mail: ccannas@unica.it This journal is ª The Royal Society of Chemistry 2011 Soft Matter , 2011, 7, 6239–6247 | 6239 Dynamic Article Links C < Soft Matter Cite this: Soft Matter , 2011, 7, 6239 www.rsc.org/softmatter PAPER Downloaded by UNIV DEGLI STUDI DI CAGLIARI on 14 December 2011 Published on 27 May 2011 on http://pubs.rsc.org | doi:10.1039/C1SM05059A View Online / Journal Homepage / Table of Contents for this issue