Delivered by Publishing Technology to: McMaster University IP: 117.253.241.100 On: Sun, 20 Mar 2016 12:02:29 Copyright: American Scientific Publishers RESEARCH ARTICLE Copyright © 2008 American Scientific Publishers All rights reserved Printed in the United States of America Journal of Nanoscience and Nanotechnology Vol. 8, 5813–5817, 2008 Evaluation of the Binding Properties of Maghemite Nanoparticle Surface-Coated with Meso-2-3-Dimercaptosuccinic Acid to Serum Albumin Andreza R. Simoni 1 , Mônica P. Garcia 2 , Ricardo B. Azevedo 2 , Sacha Braun Chaves 2 , Z. G. M. Lacava 2 , E. C. D. Lima 3 , P. C. Morais 4 , and A. C. Tedesco 1 ∗ 1 Universidade de São Paulo, FFCLRP-USP, Ribeirão Preto-SP 14040-901, Brazil 2 Universidade de Brasília, Instituto de Ciências Biológicas, Brasília-DF 70910-900, Brazil 3 Universidade Federal de Goiás, Instituto de Química, Goiânia-GO 74001-970, Brazil 4 Universidade de Brasília, Instituto de Física, Núcleo de Física Aplicada, Brasília-DF 70910-900, Brazil In this study the interaction between magnetic nanoparticles (MNPs) surface-coated with meso- 2,3-dimercaptosuccinic acid (DMSA) with both bovine serum albumin (BSA) and human serum albumin (HSA) was investigated. The binding of the MNP-DMSA was probed by the fluorescence quenching of the BSA and HSA tryptophan residue. Magnetic resonance and light microscopy analyses were carried out in in vivo tests using female Swiss mice. The binding constants (K b ) and the complex stoichiometries (n) indicate that MNP-DMSA/BSA and MNP-DMSA/HSA complexes have low association profiles. After five minutes following intravenous injection of MNP-DMSA into mice’s blood stream we found the lung firstly target by the MNP-DMSA, followed by the liver in a latter stage. This finding suggests that the nanoparticle’s DMSA-coating process probably hides the thiol group, through which albumin usually binds. This indicates that biocompatible MNP-DMSA is a very promising material system to be used as a drug delivery system (DDS), primarily for lung cancer treatment. Keywords: Magnetic Nanoparticles, Biocompatible Magnetic Fluid, Serum Albumin Proteins, Binding Constant, Nanotoxicology. 1. INTRODUCTION Biocompatible magnetic fluid (BMF) samples consist of magnetic nanoparticle (MNP) surface-coated with organic molecules stabilized as aqueous colloids at neutral pH and salinity of 0.9% NaCl (physiological medium). This spe- cial colloid has been introduced as a promising mate- rial platform for biological, medical and biotechnological applications, 1 with emphasis in the treatment of neoplastic diseases. Therefore, specific non-covalent binding of a par- ticular surface-coated MNP to biological macromolecules (proteins and lipoproteins) is a key issue in evaluating the biochemical and pharmacological responses of a magnetic drug delivery system (MDDS). 2 The efficiency of any cancer treatment based on a MDDS, such as the BMF depends upon the ability of the tumor tissue to accumulate and selectively retain the magnetic-based material. The binding of the magnetic ∗ Author to whom correspondence should be addressed. nanoparticle suspended in a BMF to various blood com- ponents influences their distribution among normal and tumor tissues, as well as their partition among the various compartments of the tumor tissue. The binding character- istic of serum albumins determines the drug biodistribution throughout the systemic circulation and is responsible for the pharmacological effects on the organism. 3 This is a very important aspect as far as the development of a biolog- ical site-specific complex based on MDDS is concerned. The meso-2,3-dimercaptosuccinic (DMSA) is a well- known molecule, often used as a chelant in the removal of heavy metals from the environmental and organisms, being considered a biologically-friend agent. 4 In part, this fact has been used to support its applications as a bio- compatible stabilizing coating for MNPs, once DMSA alone showed low toxicity in various biological systems. 5–7 In addition, due to its pharmacokinetic characteristics the DMSA molecule has been tested in several studies related to the transport and mobilization of drugs in the organism. 8 9 Considering that serum albumins are typical J. Nanosci. Nanotechnol. 2008, Vol. 8, No. 11 1533-4880/2008/8/5813/005 doi:10.1166/jnn.2008.245 5813