Facile synthesis of biocompatible superparamagnetic mesoporous nanoparticles for imageable drug delivery Tuomo Nissinen a , Simo Näkki a , Mika Latikka b , Markku Heinonen c , Timo Liimatainen d , Wujun Xu a , Robin H.A. Ras b , Olli Gröhn d , Joakim Riikonen a , Vesa-Pekka Lehto a,⇑ a Department of Applied Physics, University of Eastern Finland, 70211 Kuopio, Finland b Department of Applied Physics, Aalto University, 02150 Espoo, Finland c Department of Physics and Astronomy, University of Turku, 20014 University of Turku, Finland d A.I. Virtanen Institute for Molecular Science, University of Eastern Finland, 70211 Kuopio, Finland article info Article history: Received 5 December 2013 Received in revised form 21 March 2014 Accepted 5 April 2014 Available online 13 April 2014 Keywords: Mesoporous silicon Iron oxide Nanocomposite Nanoparticles Biomedicine abstract Superparamagnetic mesoporous silicon nanoparticles have a huge potential in drug delivery and diagnos- tics, i.e., in theranostics. These particles can carry high drug payloads, they can be targeted by external magnetic fields, they can be imaged by magnetic resonance imaging and they are biocompatible. In the present study, we demonstrate a fast and simple synthesis procedure to produce superparamagnetic mesoporous nanoparticles by precipitating iron oxide nanocrystals inside the pores of porous silicon. Subsequently, polyethylene glycol molecules with two different molecular sizes were conjugated onto the external surfaces of the composite nanoparticles to improve the colloidal stability of the suspension without compromising the magnetic properties of the composite. The developed nanoparticles possessed many advantageous properties such as superparamagnetic behavior, high T 2 relaxivity, high pore volume and modifiable surface chemistry. In addition, the present method is more straightforward and versatile than the previous methods published, preserving the pore volume larger and accessible for high drug loadings. Ó 2014 Elsevier Inc. All rights reserved. 1. Introduction Mesoporous (pore diameter 2–50 nm) drug delivery systems have stimulated considerable interest in the scientific community [1]. Mesoporous silicon (PSi) is a feasible material, since it has many desirable features such as biocompatibility [2], a modifiable surface [3–5] and high porosity, with a controllable and uniform pore size distribution as well as large surface area. The large pore volume of PSi particles enables loading of therapeutics into the pores and the mesopores can protect the payload molecules from both chem- ical and enzymatic degradation [6]. The pore walls can also be mod- ified chemically in order to achieve the desired interaction between the pore walls and the drug molecules thereby controlling the release of the drug [7,8]. Triggered release of pharmaceuticals by external stimulus has also been demonstrated [9]. Superparamagnetic iron oxide nanoparticles (SPION), are considered to be both biocompatible and safe material [10,11], and their applications in biomedicine have been investigated extensively in recent years. Superparamagnetism is an important feature, because without the presence of an external magnetic field the particles will not agglomerate, since they do not have any remanent magnetization. These, typically magnetite (Fe 3 O 4 ) or maghemite (c-Fe 2 O 3 ), particles have been shown to clearly shorten the transverse relaxation times (T 2 ) of surrounding water mole- cules through the outer sphere relaxation mechanism. This feature makes them traceable by magnetic resonance imaging (MRI) and thus beneficial for diagnostic applications [12–14]. In addition, magnetically targeted drug delivery has been investigated with promising results [15–17]. Magnetic porous nanoparticles can combine the benefits of the mesoporous materials and SPIONs, therefore, having huge potential in biomedical applications. These nanoparticles can be produced by incorporating magnetic material into the PSi matrix. This has been previously done by trapping prefabricated SPIONs inside the pores with a method utilizing oxidation of the PSi surface to expand the PSi matrix, while fixing the SPIONs inside the pores [18,19]. How- ever, drawback with this method is that the pores can become blocked by the SPIONs from both ends and a large part of the pore volume becomes inaccessible. The use of oxidation is mandatory here and this may also impose some restrictions on the surface modifications and further on the processability of the material. http://dx.doi.org/10.1016/j.micromeso.2014.04.014 1387-1811/Ó 2014 Elsevier Inc. All rights reserved. ⇑ Corresponding author. Tel.: +358 40 355 2470. E-mail address: vesa-pekka.lehto@uef.fi (V.-P. Lehto). Microporous and Mesoporous Materials 195 (2014) 2–8 Contents lists available at ScienceDirect Microporous and Mesoporous Materials journal homepage: www.elsevier.com/locate/micromeso