Colloids and Surfaces B: Biointerfaces 117 (2014) 406–413 Contents lists available at ScienceDirect Colloids and Surfaces B: Biointerfaces jo ur nal ho me p ag e: www.elsevier.com/locate/colsurfb Doxorubicin-conjugated core–shell magnetite nanoparticles as dual-targeting carriers for anticancer drug delivery Somayeh Sadighian a,b , Kobra Rostamizadeh b,c,∗ , Hassan Hosseini-Monfared a , Mehrdad Hamidi b,d a Faculty of Science, Department of Chemistry, University of Zanjan, Zanjan, Iran b Zanjan Pharmaceutical Nanotechnology Research Center, Zanjan University of Medical Sciences, Zanjan, Iran c Department of Medicinal Chemistry, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran d Department of Pharmaceutics, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran a r t i c l e i n f o Article history: Received 2 October 2013 Received in revised form 8 February 2014 Accepted 2 March 2014 Available online 12 March 2014 Keywords: Dual-targeting Nanocarrier Magnetite nanoparticles Cancer targeting Doxorubicin Conjugation a b s t r a c t The present study reports the successful synthesis of core–shell nanostructures composed of magnetite nanoparticles (Fe 3 O 4 -NPs) conjugated to the anticancer drug doxorubicin, intended for dual targeting of the drug to the tumor sites via a combination of the magnetic attraction and the pH-sensitive cleav- age of the drug–particle linkages along with a longer circulation time and reduced side effects. To improve the carrier biocompatibility, the prepared nanocarrier was, finally coated by chitosan. FT-IR analysis confirmed the synthesis of functionalized Fe 3 O 4 -NPs, doxorubicin-conjugated Fe 3 O 4 -NPs, and chitosan-coated nanocarriers. Scanning electron microscopy (SEM) indicated the formation of spherical nanostructures with the final average particle size of around 50 nm. The vibrating sample magnetometer (VSM) analysis showed that the saturation magnetization value (M s ) of carrier was 6 emu/g. The drug release behavior from the nanocarriers was investigated both in acidic and neutral buffered solutions (pH values of 5.3 and 7.4, respectively) and showed two-fold increase in the extent of drug release at pH 5.3 compared to pH 7.4 during 7 days. The results showed that the dual-targeting nanocarriers responded successfully to the external magnetic field and pH. From the results obtained, it can be concluded that this methodology can be used to target and improve therapeutic efficacy of the anticancer drugs. © 2014 Elsevier B.V. All rights reserved. 1. Introduction In recent years, there has been an increasing impetus for tar- geting therapeutic agents to specific cells of the diseased site with the aim to improve their efficiency and/or minimize the undesir- able side effects [1]. Among the numerous approaches used for this purpose, targeting based on magnetic properties using magnetic nanoparticles, mainly magnetite (Fe 3 O 4 )-based nanoparticles, is widely considered as a promising targeted delivery system due to its distinct advantages, mainly including a well-documented biosafety, ease of preparation and handling, the possibility of controlling the characteristics of the nanocarriers, availability, affordability of the materials needed for this procedure, and more ∗ Corresponding author at: Department of Medicinal Chemistry, School of Phar- macy, Zanjan University of Medical Sciences, 45139-56184 Zanjan, Iran. Tel.: +98 241 4273635; fax: +98 241 4273639. E-mail addresses: Rostamizadeh@zums.ac.ir, rostamizadeh@gmail.com (K. Rostamizadeh). importantly, possibility of targeting the drug(s) of interest to the desired location within the host body by using an external mag- netic field. Furthermore, core–shell magnetic nanoparticles have attracted much attention due to their multifunctional properties such as small size, superparamagnetism and low toxicity [2,3]. Silica-coated Fe 3 O 4 –nanoparticles are one of the most extensively used Fe 3 O 4 –nanoparticles which possess very high specific surface with abundant Si–OH or Si–NH 2 groups with ability to react with proper functional groups [4,5]. Besides the above mentioned advantages, there are a number of drawbacks against the widespread use of Fe 3 O 4 nanoparti- cles for targeted drug delivery systems. Firstly, due to the high surface-area-to-volume ratio characteristic of such nanoparticles, they tend to aggregate and form clusters with low magnetiza- tion properties. Secondly, it is shown that a major part of the naked Fe 3 O 4 nanoparticles are rapidly cleared from blood cir- culation by the reticular endothelial system (RES) before they could be able to reach the intended target site, thereby being localized in the RES organs, mainly liver [5,1]. To address these issues, one approach is to encapsulate Fe 3 O 4 nanoparticles within http://dx.doi.org/10.1016/j.colsurfb.2014.03.001 0927-7765/© 2014 Elsevier B.V. All rights reserved.