Carbohydrate Polymers 136 (2016) 71–80 Contents lists available at ScienceDirect Carbohydrate Polymers j ourna l ho me page: www.elsevier.com/locate/carbpol Alginate stabilized gold nanoparticle as multidrug carrier: Evaluation of cellular interactions and hemolytic potential Soma Dey a , M. Caroline Diana Sherly b , M.R. Rekha b , K. Sreenivasan a,∗ a Laboratory for Polymer Analysis, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Poojapura, Trivandrum 695012, India b Division of Biosurface Technology, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Poojappura, Trivandrum 695012, Kerala, India a r t i c l e i n f o Article history: Received 2 March 2015 Received in revised form 27 August 2015 Accepted 7 September 2015 Available online 9 September 2015 Keywords: Curcumin Alginate Polymer–drug conjugates Methotrexate Gold nanoparticles Confocal laser scanning microscopy a b s t r a c t This work delineates the synthesis of curcumin (Ccm) and methotrexate (MTX) conjugated biopoly- mer stabilized AuNPs (MP@Alg–Ccm AuNPs). The dual drug conjugated nano-vector was characterized by FTIR, 1 H NMR and UV–vis spectroscopic techniques. Hydrodynamic diameter and surface charge of the AuNPs were determined by DLS analysis and the spherical particles were visualized by TEM. MP@Alg–Ccm AuNPs exhibited improved cytotoxic potential against C6 glioma and MCF-7 cancer cell lines and was found to be highly hemocompatible. MP@Alg–Ccm AuNPs also exhibited active targeting efficiency against MCF-7 cancer cells due to the presence of “antifolate” drug MTX. Thus MP@Alg–Ccm AuNPs may find potential application in targeted combination chemotherapy for the treatment of cancer. The study is also interesting from the synthetic point of view because, here generation of AuNPs was done using “green chemical” alginate and dual drug conjugated AuNPs were created in two simple reaction steps using “green solvent” water. © 2015 Elsevier Ltd. All rights reserved. 1. Introduction Curcumin (Ccm) is a polyphenolic compound extracted from the rhizome of the plant Curcuma longa (Indian spice turmeric). Within the last couple of decades, extensive research work has unveiled a wide range of striking pharmacological activities in Ccm such as antioxidant, anti-inflammatory, antiproliferative and antiangio- genic activities (Aggarwal, Kumar, & Bharti, 2003; Aggarwal & Sung, 2009; Lantz, Chen, Solyom, Jolad, & Timmermann, 2005; Motterlini, Foresti, Bassi, & Green, 2000; Shi et al., 2006). It has been reported that the transcriptional nuclear factor kappa beta (NF) is the chief controller of cell proliferation, inflammation, apoptosis and resis- tance in cells and Ccm inhibits NF- resulting in blockage of the function of protein kinase C, receptor tyrosine kinase, Her-2 and epidermal growth factor to induce apoptosis. Most interestingly, development of resistance to Ccm is less likely as it induces apo- ptosis through multiple cell signaling pathways (Ravindran, Prasad, & Aggarwal, 2009). In cancer therapy Ccm can exhibit pleiotropic therapeutic effect because of its ability to inhibit multiple levels of diverse cell signaling pathways (Maher et al., 2011). Moreover, ∗ Corresponding author. E-mail address: sreeni@sctimst.ac.in (K. Sreenivasan). Ccm can also down regulate the levels of Pgp, ABCG2 and MRP-1 (three major ABC drug transporters that are mainly responsible for the development of multi drug resistance [MDR] in cancer cells) and thus it has significant role in controlling MDR (Misra & Sahoo, 2011). However, Application of Ccm as a chemotherapeutic agent is restricted due to its extremely low aqueous solubility, instabil- ity and consequent poor bioavailability (Anand, Kunnumakkara, Newman, & Aggarwal, 2007). In order to redress these problems, several approaches have been proposed and among them conjuga- tion of Ccm to hydrophilic polymers is a wise approach. Conjugation of hydrophobic drugs to suitable polymers augments aqueous sol- ubility of the drug, ensures unhindered release and offers a chance to alter drug pharmacokinetics and biodistribution which are basi- cally useful for those drugs that exhibit rapid metabolism (e.g. curcumin), faster clearance and/or off target toxicities (anticancer drugs) (Larson & Ghandehari, 2012). It has been reported that Ccm can boost the antitumor efficiency of several chemotherapeutic agents like paclitaxel and doxorubicin (Duan et al., 2012; Ganta & Amiji, 2009; Manju, Sharma, & Sreenivasan, 2011). A recent report suggests that curcumin can significantly enhance the uptake and cytotoxicity of methotrexate (MTX) in KG-1 leukemic cells (Dhanasekaran, Biswal, Sumantran, & Verma, 2013). MTX, an antimetabolite, is structurally analogous to folic acid (FA). The difference in structure between FA and MTX is due to http://dx.doi.org/10.1016/j.carbpol.2015.09.016 0144-8617/© 2015 Elsevier Ltd. All rights reserved.