Development of Magnetic Nanostructured Silica-Based Materials as Potential Vectors for Drug-Delivery Applications Manuel Arruebo, † Marta Gala ´n, † Nuria Navascue ´s, † Carlos Te ´llez, † Clara Marquina, ‡ M. Ricardo Ibarra, † and Jesu ´s Santamarı ´a* ,† Nanoscience Institute of Aragon (INA) and Materials Science Institute of Aragon (CSIC), UniVersity of Zaragoza, 50009 Zaragoza, Spain ReceiVed July 26, 2005. ReVised Manuscript ReceiVed October 31, 2005 Metallic iron nanoparticles were synthesized within micron-sized mesoporous molecular sieves (with 2.9-nm pores) and hollow silica microcapsules (pores of 2.7 and 15 nm) using several cycles of wet impregnation under vacuum, followed by drying, oxidation, and reduction steps. For iron-loaded MCM- 48, SQUID measurements revealed ferromagnetic behavior at room temperature with a magnetic moment as high as 3.40 emu/g (measured at 2 T) after four deposition cycles. Iron-loaded hollow silica microcapsules (250-nm wall thickness) showed a magnetic moment of 2.40 emu/g (at 2 T) after three deposition cycles and a coercivity as low as 12.9 Oe. Introduction Conventional cancer treatments include surgery, radiation, and chemotherapy. Surgical removal and irradiation are mainly limited by accessibility to the tumor, whereas chemotherapy is restricted by the lack of selectivity toward tumor cells, often giving rise to severe side effects in healthy tissues. Drug-delivery systems with nano- and microparticles show a clear potential for cancer treatments in view of advantages such as (i) the ability to target specific locations in the body, (ii) the ability to reduce the quantity of drug that needs to be delivered to attain a particular concentration level in the vicinity of the target, and (iii) the ability to decrease the concentration of the drug at nontarget sites. 1 As a consequence, controlled drug delivery is one of the fastest-growing segments of the pharmaceutical market, and in the United States alone, the demand is expected to grow nearly 9% annually to reach more than $82 billion by 2007. 2 The two primary challenges confronting drug-delivery systems are the achievement of a sustained delivery of the drug in the proximity of the diseased organ and the preferential targeting of malignant cells by the drug. These challenges can be addressed by acting on the characteristics of the particles and capsules that are proposed as delivery vectors. Thus, for intravenously injected particles, biocompatibility of the drug carrier is the first requirement to reduce the uptake of nano- and microparticles by the macrophages of the reticulo-endothelial system (RES) and their consequent clearance to different organs depending on the different adsorption patterns of plasma proteins (opsonins). 3 The requirement of selective targeting to minimize damage to healthy tissue can be met by promoting specific carrier- target interactions (e.g., antigen-antibody interactions) or by means of the specific physicochemical properties of the carrier (e.g., magnetism, charge, hydrophobicity/hydrophi- licity, specific affinity, pH). Different organic materials such as polymeric nanopar- ticles, liposomes, and micelles have been investigated as drug-delivery vectors. 4 However, the search for different alternatives continues in view of a variety of still unsolved problems of these systems, such as their limited chemical and mechanic stability, 5 swelling, susceptibility to micro- biological contamination, and inadequate control over the drug-release rate. On the other hand, many inorganic materials are nontoxic and biocompatible; present a high chemical and mechanical stability; and have a hydrophilic character and porous structure that can, in principle, be tailored to control the diffusion rate of an adsorbed or encapsulated drug. In this area, magnetic and nonmagnetic silica nanoparticles for drug-delivery systems can be prepared by means of the sol-gel procedure (e.g., ref 6), using silica xerogels, which are synthesized at room temperature, 7 laser pyrolysis, 8 and hydrothermal synthesis. The so-called MCMs constitute a family of silica-based mesoporous structured materials that have been scarcely investigated as drug-delivery vectors, despite their interesting characteristics. Thus, MCMs exhibit large specific surface * To whom correspondence should be addressed. E-mail: iqcatal@unizar.es. † Nanoscience Institute of Aragon (INA). ‡ Materials Science Institute of Aragon (CSIC-University of Zaragoza). (1) Ritter, J.; Ebner, A.; Daniel, K.; Stewart, K. J. Magn. Magn. Mater. 2004, 280, 184. (2) Sahoo, S. K.; Labhasetwart, V. Drug DiscoV. Today 2003, 8, 1112. (3) Mu ¨ller, R.; Lu ¨ck, M.; Harnisch, S.; Thode, K. Scientific and Clinical Applications of Magnetic Carriers; Ha ¨feli, U., Ed.; Plenum Press: New York, 1997; Chapter 10, p 141. (4) Kumar, M. R. J. Pharm. Pharm. Sci. 2000, 3, 234. (5) Barbe ´, C.; Bartlett, J.; Kong, L.; Finnie, K.; Qiang, H.; Larkin, M.; Calleja, S.; Bush, A.; Calleja G. AdV. Mater. 2004, 16, 1959. (6) Veith, S. R.; Perren, M.; Pratsinis, S. E. J. Colloid Interface Sci. 2005, 283, 495. (7) Kortesuo, P.; Ahola, M.; Kangas, M.; Yli-Urpo, A.; Kiesvaara, J.; Marvola, M. Int. J. Pharmac. 2001, 221, 107. (8) Bomatı ´-Miguel, O.; Leconte, Y.; Morales, M. P.; Herlin-Boime, N.; Veintemillas-Verdaguer, S. J. Magn. Magn. Mater. 2005, 272-275, 290. 1911 Chem. Mater. 2006, 18, 1911-1919 10.1021/cm051646z CCC: $33.50 © 2006 American Chemical Society Published on Web 03/14/2006