Comparative Evaluation of Heating Ability and Biocompatibility of Different Ferrite-Based Magnetic Fluids for Hyperthermia Application Pallab Pradhan, 1 Jyotsnendu Giri, 2 Gopal Samanta, 3 Haladhar Dev Sarma, 4 Kaushala Prasad Mishra, 4 Jayesh Bellare, 1 Rinti Banerjee, 1 Dhirendra Bahadur 2 1 School of Biosciences and Bioengineering, Indian Institute of Technology, Mumbai 400076, India 2 Department of Metallurgical Engineering and Materials Science, Indian Institute of Technology, Mumbai 400076, India 3 Department of Veterinary Surgery and Radiology, West Bengal University of Animal and Fishery Sciences, Kolkata 700037, India 4 Radiation Biology and Health Science Division, Bhabha Atomic Research Centre, Mumbai 400085, India Received 12 November 2005; revised 31 March 2006; accepted 10 April 2006 Published online 21 August 2006 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/jbm.b.30630 Abstract: In this study, lauric acid-coated, superparamagnetic, nanoparticle-based magnetic fluids of different ferrites (Fe 3 O 4 , MnFe 2 O 4 , and CoFe 2 O 4 ) were prepared and compared in terms of heating ability and biocompatibility to evaluate the feasibility of use in hyperthermia treatment of cancer. All the magnetic fluids prepared had particles of average sizes 9–11 nm. Heating ability of these magnetic fluids was evaluated by calorimetric measurement of specific absorption rate (SAR) at 300 kHz frequency and 15 kA/m field. Fe 3 O 4 and MnFe 2 O 4 showed higher SAR (120 and 97 W/g of ferrite, respectively) than CoFe 2 O 4 (37 W/g of ferrite) . In vitro study on BHK 21 cell lines showed dose-dependent cell viability for all the magnetic fluids. Threshold-biocompatible ferrite concentration for all the magnetic fluids was 0.1 mg/mL. Above 0.2 mg/mL, CoFe 2 O 4 was more toxic than the other magnetic fluids. On intravenous injection of different doses (50, 200, and 400 mg/kg body weight) of magnetic fluids in mice, no significant changes in hematological and biochemical parameters were observed for Fe 3 O 4 and MnFe 2 O 4 . With CoFe 2 O 4 , an increase in SGPT levels at a dose rate of 400 mg/kg body weight was observed, indicating its mild hepatotoxic effect. However, histology of different vital organs showed no pathological changes for all the three magnetic fluids. Further, long term in vivo evaluation of biocompatibility of the lauric acid-coated ferrites is warranted. This study shows that lauric acid-coated, superparamagnetic Fe 3 O 4 and MnFe 2 O 4 may be used for hyperthermia treatment and are to be preferred over CoFe 2 O 4. ' 2006 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 81B: 12–22, 2007 Keywords: magnetic nanoparticle; magnetic fluid; biocompatibility; specific absorption rate; hyperthermia INTRODUCTION In recent years, magnetic particles have generated a lot of in- terest in the biomedical applications, like MRI contrast enhancement, magnetic separation, drug delivery, and hyper- thermia. 1–3 One of the prospective applications of magnetic nanoparticles is hyperthermia treatment of cancer. 4,5 In clini- cal hyperthermia, efforts are made to optimize the thermal ho- mogeneity at 42–468C in the tumor tissue by advanced therapy and thermometry systems. Magnetic materials with Curie temperature (T c ) between 42 and 608C are the best can- didates for effective treatment, since they act as in vivo tem- perature control switches, preventing over-heating. 6 For hyperthermia, superparamagnetic as well as ferrimagnetic par- ticles, such as Fe 3 O 4 or c-Fe 2 O 3 , have been explored exten- sively. 4,7,8 The systems M 1x Zn x Fe 2 O 4 (M ¼ Mn, Co), which have versatile magnetic properties and Curie temperature (T c ) obtained by substitution of nonmagnetic cations, have not yet been explored. 9,10 The heating ability and biocompatibility of these magnetic fluids need to be investigated. Heating ability of magnetic fluid which is measured by specific absorption rate (SAR) depends on physical (particle size, shape, and dis- tribution) as well as magnetic properties of particles. 11 There Correspondence to: D. Bahadur (e-mail: dhirenb@iitb.ac.in) Contract grant sponsor: Department of Biotechnology (DBT) and Department of Science and Technology (DST), India ' 2006 Wiley Periodicals, Inc. 12