Colloids and Surfaces B: Biointerfaces 116 (2014) 219–227 Contents lists available at ScienceDirect Colloids and Surfaces B: Biointerfaces journal homepage: www.elsevier.com/locate/colsurfb Antitumor activity of galactoxyloglucan-gold nanoparticles against murine ascites and solid carcinoma Manu M. Joseph a , S.R. Aravind a , Suraj K. George b , K. Raveendran Pillai c , S. Mini d , T.T. Sreelekha a,∗ a Laboratory of Biopharmaceuticals and Nanomedicine, Division of Cancer Research, Regional Cancer Centre, Trivandrum, Kerala, India b Dept. of Hematopathology, UT MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, 77030, TX, USA c Department of Pathology, Regional Cancer Centre, Trivandrum, Kerala, India d Department of Biochemistry, University of Kerala, Trivandrum, Kerala, India article info Article history: Received 29 October 2013 Received in revised form 2 December 2013 Accepted 27 December 2013 Available online 9 January 2014 Keywords: Anticancer Dalton’s Lymphoma Ascites Ehrlich’s Ascites Carcinoma Polysaccharide Galactoxyloglucan Gold nanoparticle Tamarindus indica abstract Galactoxyloglucan polysaccharide (PST001), isolated from the seed kernels of Tamarindus indica (Ti), was used both as reducing and capping agent for the preparation of gold nanoparticles (PST-Gold) of 20 nm size. The present study evaluated the anticancer effects of the PST-Gold nanoparticles both in vitro and in vivo. The cytotoxicity was evaluated in the murine cancer cell lines, Dalton’s lymphoma ascites (DLA) and Ehrlich’s ascites carcinoma (EAC). Galactoxyloglucan-gold nanoparticles (PST-Gold) not only retained the anticancer effects of PST001, but also showed enhanced cytotoxicity via induction of apoptosis even at lower doses and lesser incubation times. In vivo antitumor activity was tested in DLA and EAC murine ascites and EAC solid-tumor syngeneic mouse models. PST-Gold nanoparticles reduced tumor burden and increased median survival and life span significantly in both tumor models compared to the con- trols. The PST-Gold nanoparticles were very effective as a chemopreventive agent, showing the best overall response when administered prior to tumor induction. In the case of solid tumors, intratumoral administration of the PST-Gold nanoparticles yielded significant results with regard to survival and incre- ment in lifespan as compared to intraperitoneal mode of drug administration. Further studies in higher animal models and in patients at high-risk for recurrence are warranted to fully explore and develop the potential of PST-Gold nanoconjugates as a chemopreventive and therapeutic anti-cancer agent. © 2014 Elsevier B.V. All rights reserved. 1. Introduction Cancer is a major cause of mortality worldwide and, in spite of the extraordinary effort and money spent over the past sev- eral decades, successful eradication and control remains intangible [1]. Cancer is described as a heterogeneous collection of cells that evolve in tumor microenvironments with complex ecologies [2]. The rapid progression of human cancers is related to the evasion of the body’s immune surveillance mechanisms by tumor cells through the secretion of immunosuppressive factors that modify the host immune response. Currently available chemotherapeutic modalities also suppress the immune system, predisposing can- cer patients to secondary infections [3]. In this regard, there is a ∗ Corresponding author at: Scientific Officer Grade 1, Division of Cancer Research, Regional Cancer Centre (RCC), Trivandrum-11, Kerala, India. Tel.: +91 4712522378; fax: +91 4712447454. E-mail addresses: lekhasree64@yahoo.co.in, lekhasree@rcctvm.org, ttsreelekha@gmail.com (T.T. Sreelekha). significant unmet need for novel pharmaceutical agents with tumor selectivity and specificity, but with limited side effects. Tamarindus indica (Ti), a tree of the Leguminosae family, is widely grown in India and is associated with numerous ben- eficial effects. Previous studies have shown the predominant composition of the Ti seed kernel to be a polysaccharide, galactoxy- loglucan; ˛ (1 → 4)-- D-glucan backbone substituted with side chains of d-xylopyranose and -d-galactopyranosyl (1 → 2)--d- xylopyranose linked (1 → 6) to glucose residues [4,5]. Antioxidant, antitumor, immunomodulatory, antimicrobial, antiulcer, and sev- eral other pharmacological activities from various polysaccharides have been reported [6–8]. Among the biopharmacological proper- ties of polysaccharides, immunomodulatory and antitumor effects are of high priority and the majority of these agents act as biological response modifiers, which enhance immunity [9]. Ti polysaccha- rides have widespread utility in anticancer, immunomodulatory, antiviral, antioxidant and other pharmacological applications including its use as artificial tears in modern medicine [10–12]. They are biocompatible, biodegradable, highly viscous, and ther- mally stable polymers with a broad range of pH tolerance and adhesiveness [13]. Galactoxyloglucan PST001, extracted from the 0927-7765/$ – see front matter © 2014 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.colsurfb.2013.12.058