4194 IEEE TRANSACTIONS ON MAGNETICS, VOL. 41, NO. 10, OCTOBER 2005 Novel Superparamagnetic Core(Shell) Nanoparticles for Magnetic Targeted Drug Delivery and Hyperthermia Treatment Palash Gangopadhyay, Sébastien Gallet, Edith Franz, André Persoons, and Thierry Verbiest Center for Molecular Electronics and Photonics, Molecular and Nano Materials, Department of Chemistry, Catholic University of Leuven, Heverlee 3001, Belgium Superparamagnetic - core(shell) nanoparticles with narrow size distribution and different shell thicknesses are synthe- sized. On conjugation with serum albumin, this set of particles forms an ideal candidate to be used in magnetic targeted drug delivery and hyperthermia treatment. In this contribution, the synthesis and characterizations of their size, optical, and magnetic properties are reported. It has also been shown that using different shell thicknesses, it is possible to tune not only the plasmon response of the gold shell but also the magnetic property of these superparamagnetic nanoparticles. Index Terms—Core(shell) nanoparticles, hyperthermia, maghemite (gold), magnetic targeted drug delivery. I. INTRODUCTION T HE last few decades have witnessed a tremendous increase in the interest to use ferrofluids and ferrofluid–drug con- jugates in magnetically guided drug delivery in loco regional treatment of cancer/tumor [1]–[3]. Guided transport of drugs to the target organ/tissue allows one to create an optimum thera- peutic concentration of the drug while keeping the total injection dose low and minimizing side effects. On the other hand, mag- netic fluid hyperthermia increases the efficacy of chemotherapy [4]. However, the commercially available ferrofluids suffer from their irregular shape and have large polydisperse particles with very weak magnetic response. Very few of the ferrofluid–drug conjugates reported till date have reached actual clinical trial stages [5]. There is a great need for preparing smart particles that can combine all the functions deemed for ferrofluid–drug conjugates along with laser-induced hyperthermia. In 1960, Freeman et al. pioneered the concept of magnetic targeted drug delivery using fine iron particles. Since then, mag- netic targeted drug delivery has become an attractive field of re- search [6]. Although there are different opinions about the ideal size of the magnetic nanoparticles for their use in drug delivery, a core diameter of 10 nm is the smallest that has been proposed so far [6]. Furthermore, the nanoparticles need to be resistant to the autoimmune response from the body to have long circula- tion time inside. Hyperthermia is a therapeutic procedure where a magnetic fluid is used to increase temperature loco regionally inside the body with the help of an external alternating current (ac) mag- netic field, usually employed along with other cancer treatment procedures. Heating occurs due to various loss processes during reorientation of the magnetization of the magnetic nanoparti- cles. In the case of laser-induced hyperthermia, one uses a mate- rial that absorbs in the near-infrared (NIR) region, and upon illu- minating with NIR lasers, the material heats up. Recently, silica Digital Object Identifier 10.1109/TMAG.2005.854805 (gold) core(shell) particles, absorbing in the NIR region, have been proposed for such treatment; however, it fails to promise loco regional treatment [7]. Iron oxide [maghemite ( - ) and magnetite ( )] nanoparticles are most commonly employed for magnetic targeted drug delivery and hyperthermia treatment. In this work maghemite nanoparticles have been coated with gold to form a core(shell) particles in order to achieve 1) a high degree of biofunctionalization made possible by the gold surface, 2) low toxicity, and 3) the possibility of employing these particles in laser-induced hyperthermia treatment using the red-shifted plasmon response from gold shell in combination with mag- netic hyperthermia treatment. Interestingly, these particles also provide unique systems to study diamagnetic shielding on magnetic nanoparticles. In this report, experiments on maghemite (gold) superparam- agnetic core(shell) nanoparticles conjugated to human/bovine serum albumin are presented. Fig. 1 presents a cartoon represen- tation of a cross section of such a particle. The superparamagnetic maghemite - nanoparticles are 9 nm in diameter. The proposed novel method to coat them with gold allows us to vary the shell thickness resulting in particles with overall diameter from 15 to 30 nm [Fig. 2(a)], thus pushing the gold shell plasmon resonance to the 700–800 nm region [Fig. 2(b)]. This, in turn, makes these particles suitable for use in laser-induced hyperthermia and, if needed, in conjugation with conventional ac magnetic field-induced hyperthermia treatments. These su- perparamagnetic [Fig. 2(c)] particles can be prepared in gram scale quantity and are water soluble. These core(shell) parti- cles have been coated with serum albumin proteins with the aim of making them more resistant to the body autoimmune response. II. EXPERIMENTAL PROCEDURE Synthesis of 9 nm - nanoparticles has been re- ported previously [8]. In a typical preparation of water-soluble - core(shell) nanoparticles, 0.12 g of - particles is dissolved in 200 mL of dimethylformamide (DMF) 0018-9464/$20.00 © 2005 IEEE