International Journal of Biological Macromolecules 80 (2015) 48–56 Contents lists available at ScienceDirect International Journal of Biological Macromolecules j ourna l ho me pa g e: www.elsevier.com/locate/ijbiomac Natural polysaccharide functionalized gold nanoparticles as biocompatible drug delivery carrier Deep Pooja a,d , Sravani Panyaram a , Hitesh Kulhari a,b,c , Bharathi Reddy a , Shyam S. Rachamalla d , Ramakrishna Sistla a,∗ a Medicinal Chemistry & Pharmacology Division, CSIR-Indian Institute of Chemical Technology, Hyderabad, India b IICT-RMIT Research Centre, CSIR-Indian Institute of Chemical Technology, Hyderabad, India c School of Applied Sciences, RMIT University, Melbourne, Australia d Faculty of Pharmacy, College of Technology, Osmania University, Hyderabad, India a r t i c l e i n f o Article history: Received 15 May 2015 Received in revised form 8 June 2015 Accepted 15 June 2015 Available online 18 June 2015 Keywords: Gold nanoparticles Gum karaya Biocompatibility Gemcitabine hydrochloride Anticancer activity a b s t r a c t Biocompatibility is one of the major concerns with inorganic nanoparticles for their applications as drug delivery system. Natural compounds such as sugars, hydrocolloids and plant extracts have shown poten- tial for the green synthesis of biocompatible gold nanoparticles. In this study, we report the synthesis of gum karaya (GK) stabilized gold nanoparticles (GKNP) and the application of prepared nanoparticles in the delivery of anticancer drugs. GKNP were characterized using different analytical techniques. GKNP exhib- ited high biocompatibility during cell survival study against CHO normal ovary cells and A549 human non-small cell lung cancer cells and during hemolytic toxicity studies. Gemcitabine hydrochloride (GEM), an anticancer drug, was loaded on the surface of nanoparticles with 19.2% drug loading efficiency. GEM loaded nanoparticles (GEM-GNP) showed better inhibition of growth of cancer cells in anti-proliferation and clonogenic assays than native GEM. This effect was correlated with higher reactive oxygen species generation by GEM-GNP in A549 cells than native GEM. In summary, GK has significant potential in the synthesis of biocompatible gold nanoparticles that could be used as prospective drug delivery carrier for anticancer drugs. © 2015 Elsevier B.V. All rights reserved. 1. Introduction In recent years, inorganic nanoparticles have attracted much attention in the area of bio imaging, drug delivery and other ther- apeutic and diagnostic applications. A definite size and unique surface composition make them suitable carriers for the develop- ment of targeted drug delivery system. Commonly used inorganic nanoparticles include metal (gold, silver, and platinum) nanopar- ticles, quantum dots, carbon nanotubes, iron oxide magnetic nanoparticles and ceramic nanoparticles [1,2]. Among these inorganic nanoparticles, gold nanoparticles are most commonly investigated due to their unique optical-electronic properties, ease of synthesis, opportunity for surface modification, non-cytotoxicity and biocompatibility [3,4]. Gold nanoparticles can be synthesized using physical, chemical and biological approaches ∗ Corresponding author at: Medicinal Chemistry and Pharmacology Divi- sion, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India. Tel.: +91 40 27193753. E-mail address: sistla@iict.res.in (R. Sistla). [1]. The chemical synthesis of gold nanoparticles relies on the reduction of electropositive gold (Au 3+ ) to neutral gold atoms. Several chemical agents are used as reducing agents in prepa- ration of gold nanoparticles. Phosphorus was the first reducing agent, used by Michael Faradey to prepare colloidal gold, and after that sodium borohydride [5], citrate [6,7], polymers like poly (N- vinyl-2-pyrrolidone) [8,9], block copolymers [10], and G5 PAMAM dendrimers [11], were used to prepare and stabilize the gold nanoparticles. However, the toxicity and involvement of organic solvent are the major limitations of these reducing agents. To overcome the above problems, natural compounds like gums [12–14], proteins [15], glucan [16], hemicellulose-arabinoxylan [17], hyluronan [18], and chitosan [19,20] have been encour- aged in gold nanoparticle preparation. Gums are high molecular weight, hydrophilic polymers and are composed of monosaccha- rides attached with glycosidic bonds. Natural gums are obtained from plants and generally present in the intracellular parts of the plant or as extracellular exudates. Gum karaya (GK) is the dried exudates obtained from Sterculia urens Roxd and other related species of Sterculia (family Sterculiaceae) or Cochlosper- mum gossypium AP De Candolle or other species of C kunth (family http://dx.doi.org/10.1016/j.ijbiomac.2015.06.022 0141-8130/© 2015 Elsevier B.V. All rights reserved.