Published: January 25, 2011 r2011 American Chemical Society 1003 dx.doi.org/10.1021/jp1109916 | J. Phys. Chem. A 2011, 115, 1003–1008 ARTICLE pubs.acs.org/JPCA Spectroscopic Study of Maghemite Nanoparticles Surface-Grafted with DMSA Maria A. G. Soler,* ,† Emilia C. D. Lima, ‡ Eloiza S. Nunes, ‡ Fabio L. R. Silva, † Aderbal C. Oliveira, † Ricardo B. Azevedo, § and Paulo C. Morais † † Instituto de Física, Universidade de Brasília, Brasília DF 70910-900, Brazil ‡ Instituto de Química, Universidade Federal de Goi  as, Goi ^ ania GO 74001-970, Brazil § Instituto de Ci ^ encias Biologicas, Universidade de Brasília, Brasília DF 70910-900, Brazil ABSTRACT: Nanosized maghemite (below 10 nm average diameter), surface-functionalized with meso-2,3-dimercapto- succinic acid (DMSA), was investigated with respect to the content of DMSA molecules attached onto its surface and the onset of S-S bridges due to oxidation of neighboring S-H groups. To support our investigation, we introduced the use of photoacoustic spectroscopy to monitor thiol groups (S-H) conjugated with Raman spectroscopy to monitor the disulfide bridges (S-S). The normalized intensity (N R ) of the Raman feature peaking at 500 cm -1 was used to probe the S-S bridge whereas the normalized intensity (N P ) of the photoacoustic band-S (0.42-0.65 μm) was used to probe the S-H moiety. The perfect linearity observed in the N R versus (1 - N P ) plot strongly supports the oxidation process involving neighboring S-H groups as the DMSA surface grafting coefficient increases whereas the approach used in this report allows the evaluation of the [S-H]/[S-S] ratio. The observation of the reduction of the hydrodynamic diameter as the nominal DMSA-grafting increases supports the proposed model picture, in which the intraparticle (interparticle) S-S bridging takes place at higher (lower) DMSA- grafting values. ’ INTRODUCTION The surface functionalization of bare superparamagnetic iron oxide (SPIO) particles using previously selected molecules is a key point while tailoring these materials for both industrial and medical applications. Commercial insulating oil containing sur- face-dressed SPIO particles in suspension has been successfully prepared for improvement of transformer’s cooling efficiency. 1 High-resolution MRI technology can be realized by magnetically tagging tumor cells using SPIO-based materials. 2,3 Chemother- apeutic agents can be attached to surface-functionalized SPIO particles, thus allowing their site localization (tumor region) via application of magnetic field gradients after injection into the blood circulation and/or nearby the tumor site. 4 Indeed, the use of surface-functionalized SPIO particles as a material platform to fabricate complex magnetic drug delivery systems has attracted considerable interest in recent years. 5-7 While developing surface-functionalized SPIO-based systems addressed to medical applications, one has to carefully take into account basic aspects, among others the chemical characteristics of the molecular coating layer and the physical properties of the SPIO core. It is worth notice that in many applications the SPIO surface functionalization represents just the intermediate step toward binding bioactive molecules in a latter stage. 8,9 The chemical and the physical characteristics of the end product depend on both the SPIO synthesis route and the protocols used in the surface functionalization. 10 The coating and the core material characteristics not only affect the efficiency of the SPIO-based product while addressed to a particular application but also influence cell internalization, biodistribution, nanotoxi- city, metabolization, and clearance parameters. 11 Among the surface-coatings used nowadays, meso-2,3-dimer- captosuccinic acid (DMSA) has been successfully employed in the surface functionalization of SPIO-based materials. 12-16 In addition, DMSA-coating also allows efficient transfer of the func- tionalized SPIO particles from organic to aqueous phase, 7,17-19 providing improved stability and easy conjugation to bioactive molecules. Biodistribution investigation of DMSA-coated magne- tite nanoparticles intravenously injected in mice was conducted using light microscopy and magnetic resonance, revealing en- hanced organ specificity to lung, which collects almost all the particles 30 min after the animal’s injection. 13 The preferential uptake of DMSA functionalized SPIO particles by lung was confirmed in an extended time window experiment, showing that organ inflammation was actually induced by the treatment. 14 In nanosized iron-based SPIO particles, DMSA molecules are known to be covalently bonded at iron sites onto the particle’s Received: July 12, 2010 Revised: December 27, 2010