Colloids and Surfaces B: Biointerfaces 107 (2013) 27–34 Contents lists available at SciVerse ScienceDirect Colloids and Surfaces B: Biointerfaces jou rn al h om epage: www.elsevier.com/locate/colsurfb One pot synthesis of gold nanoparticles and application in chemotherapy of wild and resistant type visceral leishmaniasis Suvadra Das a , Partha Roy a , Subhasish Mondal b , Tanmoy Bera b , Arup Mukherjee a,∗ a Department of Chemical Technology, University of Calcutta, 92, A.P.C. Road, Kolkata 700009, West Bengal, India b Department of Pharmaceutical Technology, Jadavpur University, Kolkata, West Bengal, India a r t i c l e i n f o Article history: Received 5 November 2012 Received in revised form 11 January 2013 Accepted 21 January 2013 Available online 9 February 2013 Keywords: Quercetin Gold nanoparticle Visceral leishmaniasis Flavonoid a b s t r a c t Gold nanoparticles (Aunp) through biogenetic processes have induced enormous interest for lower tox- icity and precise applications. A rapid, one pot synthesis for uniformly sized gold nanoparticles was developed using polyphenolic compound quercetin. Reduction process was followed at low tempera- tures in a simple bath type sonicator. Nanoparticle plasmon response was recorded at 540 nm and the average size in TEM was observed at 15.07 nm. Detailed X-ray diffraction (XRD) observations proved fcc crystalline structure of metallic gold and the Fourier transform infrared (FTIR) analysis has confirmed nanoparticles conjugation with quercetin. Leishmaniasis, is a neglected tropical disease (NTD) classified by the World Health Organization (WHO). The leishmanial parasite multiply in host macrophages and most strains have developed drug resis- tance to available chemotherapeutics. Drug delivery is therefore a major problem in macrophage specific leishmanial parasite infections. New quercetin conjugated gold nanoparticles (QAunp) were success- fully evaluated for the first time against leishmanial macrophage infections. Antileishmanial efficiency of QAunp was established against wild type (IC 50 15 ± 3), sodium stibogluconate resistant strain (IC 50 40 ± 8) and the paramomycin resistant (IC 50 30 ± 6) strains. Macrophage uptake of QAunp was complete within an hour as observed in TEM experiments. © 2013 Elsevier B.V. All rights reserved. 1. Introduction Non viral nanoparticulate systems are increasingly important tools in therapeutics due to lower toxicity and specialized cell tar- geting. Advantages of nanoparticles reside in facile synthesis and possibilities for biomolecular conjugation. Metal nanoparticles like gold are stable in systemic circulation and targeted delivery using gold nanoparticles are a significant possibility [1]. Gold nanopar- ticles (Aunp) are veritable tools in therapeutics and were applied earlier in drug delivery, diagnosis and imaging [2,3]. Different plant extracts can also be used in synthesis of functionalized nanoparti- cles [4]. Size and shape controlled synthesis of gold nanoparticles from ionic salts are known [5]. Leishmaniasis is a parasitic disease. Among different leishma- nial infections, visceral leishmaniasis (VL) caused by Leishmania donovini is the most threatening one. Once infested, leishmanial parasites rapidly locate themselves in vertebrate macrophages in a proliferative non flageller amastigote form [6]. The disease is clas- sified as neglected tropical disease (NTD) and WHO has put an ardent appeal for development of drug candidates and innovative ∗ Corresponding author. Tel.: +91 33 23508386/91 33 23508387; fax: +91 33 23519755. E-mail addresses: arupm1234@gmail.com, hdct1@yahoo.co.in (A. Mukherjee). delivery systems for control and abatement of leishmaniasis [7]. Most strains of leishmaniasis are however reported to be resistant to standard chemotherapeutics like antimonials and paramomycin and that has made the task very challenging. Size dependent macrophage uptake of gold nanoparticles is reported relatively recently [8,9]. Nanoparticle gold in a particular size range is known to induce dose dependent oxida- tion imbalance in autophagous cells [10]. Plant derived known chemical entities (KCE) like andrographolide, quercetin and lute- olin on the other hand are currently considered as alternative chemotherapeutics against leishmanial infections [11,12]. These compounds interfere in cellular oxidative processes but present a systemic transport problem due to low water solubility. New nano-bio-conjugate gold was therefore conceived for the first time as a stratagem against macrophage infested leishmanial infections. This work was primarily organized to develop flavonoid conju- gated gold nanoparticle for application against wild and resistant type leishmanial amastigotes. The work was also meant to develop facile bio-catalytic techniques for synthesis of quercetin function- alized gold nanoparticles (QAunp). Quercetin, a widely available plant flavonoid was used successfully both as a bio reducing agent for Au +3 and molecular bioconjugation in situ. Macrophage uptake of new gold nanoparticles and anti-leishmanial efficacy were inves- tigated positively against both the wild and resistant type parasites. 0927-7765/$ – see front matter © 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.colsurfb.2013.01.061