Decanethiol functionalized silver nanoparticles are new powerful leishmanicidals in vitro

  • A. P. Isaac-Márquez
  • P. Talamás-Rohana
  • N. Galindo-Sevilla
  • S. E. Gaitan-Puch
  • N. A. Díaz-Díaz
  • G. A. Hernández-Ballina
  • C. M. Lezama-Dávila
Original Paper


We evaluated, for the first time, the leishmanicidal potential of decanethiol functionalized silver nanoparticles (AgNps–SCH) on promastigotes and amastigotes of different strains and species of Leishmania: L. mexicana and L. major isolated from different patients suffering from localized cutaneous leishmaniasis (CL) and L. mexicana isolated from a patient suffering from diffuse cutaneous leishmaniasis (DCL). We recorded the kinetics of promastigote growth by daily parasite counting for 5 days, promastigote mobility, parasite reproduction by CFSE staining’s protocol and promastigote killing using the propidium iodide assay. We also recorded IC50’s of promastigotes and amastigotes, therapeutic index, and cytotoxicity by co-culturing macrophages with AgNps–SCH or sodium stibogluconate (Sb) used as reference drug. We used Sb as a reference drug since it is used as the first line treatment for all different types of leishmaniasis. At concentrations 10,000 times lower than those used with Sb, AgNps–SCH had a remarkable leishmanicidal effect in all tested strains of parasites and there was no toxicity to J774A.1 macrophages since > 85% were viable at the concentrations used. Therapeutic index was about 20,000 fold greater than the corresponding one for Sb treated cells. AgNps–SCH inhibited > 80% promastigote proliferation in all tested parasites. These results demonstrate there is a high leishmanicidal potential of AgNps–SCH at concentrations of 0.04 µM. Although more studies are needed, including in vivo testing of AgNps–SCH against different types of leishmaniasis, they can be considered a potential new treatment alternative.

Graphical Abstract


Decanethiol functionalized silver nanoparticles Leishmaniasis Silver nanoparticles L. mexicana L. major Leishmanicidal activity 



This study was financially supported by Consejo Nacional de Ciencia y Tecnología de México (CONACYT) and Universidad Autónoma de Campeche. Authors are thankful to Vania Isaac-Márquez for her excellent graphic design work.


  1. Abamor ES, Allahverdiyev AM (2016) A nanotechnology based new approach for chemotherapy of cutaneous leishmaniasis: TIO2@AG nanoparticles—Nigella sativa oil combinations. Exp Parasitol 166:150–163. CrossRefGoogle Scholar
  2. Ahmad A, Wei Y, Syed F, Khan S, Khan GM, Tahir K, Khan AU, Raza M, Khan FU, Yuan Q (2016) Isatis tinctoria mediated synthesis of amphotericin B-bound silver nanoparticles with enhanced photoinduced antileishmanial activity: a novel green approach. J Photochem Photobiol B 161:17–24. CrossRefGoogle Scholar
  3. Allahverdiyev AM, Abamor ES, Bagirova M, Ustundag CB, Kaya C, Rafailovich M (2011) Antileishmanial effect of silver nanoparticles and their enhanced antiparasitic activity under ultraviolet light. Int J Nanomed 6:2705–2714. CrossRefGoogle Scholar
  4. Allahverdiyev AM, Abamor ES, Bagirova M, Baydar SY, Aters SC, Kaya F, Rafailovich M (2013) Investigation of antileishmanial activities of Tio2@Ag nanoparticles on biological properties of L. tropica and L. infantum parasites, in vitro. Exp Parasitol 135:55–63. CrossRefGoogle Scholar
  5. Arvizo OR, Miranda OR, Thompson MA, Pabelick CM, Bhattacharya RB, Robertson JD, Rotello VM, Prakash YS, Mukherjee P (2010) Effect of nanoparticle surface charge at the plasma membrane and beyond. Nano Letters 10:2543–2548. CrossRefGoogle Scholar
  6. Carlson C, Hussain SM, Schrand AM, Braydich-Stolle LK, Hess KL, Jones RL, Schlager JJ (2008) Unique cellular interaction of silver nanoparticles: size-dependent generation of reactive oxygen species. J Phys Chem B 112:13608–13619. CrossRefGoogle Scholar
  7. Dai X, Guo Q, Zhao Y, Zhang P, Zhang T, Zhang X, Li C (2016) Functional silver nanoparticle as a benign antimicrobial agent that eradicates antibiotic-resistant bacteria and promotes wound healing. ACS Appl Mater Interfaces 8:25798–25807. CrossRefGoogle Scholar
  8. Dar AA, Enjamuri N, Shadab M, Ali N, Khan AT (2015) Synthesis of unsymmetrical sulfides and their oxidation to sulfones to discover potent antileishmanial agents. ACS Comb Sci 17:671–681. CrossRefGoogle Scholar
  9. Foglieni C, Meoni C, Davalli AM (2001) Fluorescent dyes for cell viability: an application on prefixed conditions. Histochem Cell Biol 115(3):223–229Google Scholar
  10. Gonzalez-Carter DA, Leo BF, Ruenraroengsak P, Chen S, Goode AE, Theodorou IG, Chung KF, Carzaniga R, Shaffer MS, Dexter DT, Ryan MP, Porter AE (2017) Silver nanoparticles reduce brain inflammation and related neurotoxicity through induction of H2S-synthesizing enzymes. Sci Rep 7:42871. CrossRefGoogle Scholar
  11. Gutiérrez V, Seabra AB, Reguera RM, Khandare J, Calderón M (2016) New approaches from nanomedicine for treating leishmaniasis. Chem Soc Rev 45:152–168. CrossRefGoogle Scholar
  12. Isaac-Márquez AP, Lezama-Dávila CM (2003) Detection of pathogenic bacteria in skin lesions of patients with chiclero’s ulcer. Reluctant response to antimonial treatment. Mem Inst Oswaldo Cruz 98:1093–1095. CrossRefGoogle Scholar
  13. Isaac-Márquez AP, McChesney JD, Nanayakara NP, Satoskar AR, Lezama-Dávila CM (2010) Leishmanicidal activity of racemic +/- 8-[(4-amino-1-methylbutyl)amino]-6-methoxy-4-methyl-5-[3,4-dichlorophenoxy]quinoline. Nat Prod Commun 5:387–390Google Scholar
  14. Jebali A, Kazemi B (2013) Nano-based antileishmanial agents: a toxicological study on nanoparticles for future treatment of cutaneous leishmaniasis. Toxicol In Vitro 27:1896–1904. CrossRefGoogle Scholar
  15. Kalangi SK, Dayakar A, Gangappa D, Sathyavathi R, Maurya RS, Narayana Rao D (2016) Biocompatible silver nanoparticles reduced from Anethum graveolens leaf extract augments the antileishmanial efficacy of miltefosine. Exp Parasitol 170:184–192. CrossRefGoogle Scholar
  16. Kumar R, Engwerda C (2014) Vaccines to prevent leishmaniasis. Clin Transl Immunology 3:e13. CrossRefGoogle Scholar
  17. Lezama-Dávila CM, Isaac-Márquez AP (2013) Extracto de Pentalinon andrieuxii Müeller-Argoviensis encapsulado en hidroxietilcelulosa para el tratamiento de la leishmaniasis. Patent registry in México (IMPI) no. MX/2013/103063Google Scholar
  18. Lezama-Dávila CM, Isaac-Márquez AP, Kapadia G, Owens K, Oghumu S, Beverley S, Satoskar AR (2012) Leishmanicidal activity of two naphthoquinones against Leishmania donovani. Biol Pharm Bull 35:1761–1764CrossRefGoogle Scholar
  19. Lezama-Dávila CM, Pan L, Isaac-Márquez AP, Terrazas C, Oghumu S, Isaac-Márquez R, Pech-Dzib MY, Barbi J, Calomeni E, Parinandi N, Kinghorn AD, Satoskar AR (2014) Pentalinon andrieuxii root extract is effective in the topical treatment of cutaneous leishmaniasis caused by Leishmania mexicana. Phytother Res 28:909–916. CrossRefGoogle Scholar
  20. Lezama-Dávila CM, McChesney JD, Bastos JK, Miranda MA, Tossi RF, da Costa JC, Bentley MV, Gaitan-Puch SE, Isaac-Márquez AP (2016) A new antileishmanial preparation of combined solamargine and solasonine heals cutaneous leishmaniasis through different immunochemical pathways. Antimicrob Agents Chemother 60:2732–2738. CrossRefGoogle Scholar
  21. Li Y, Lin Z, Zhao M, Xu T, Wang C, Hua L, Wang H, Xia H, Zhu B (2016) Silver nanoparticle based codelivery of oseltamivir to inhibit the activity of the H1N1 influenza virus through ROS-mediated signaling pathways. ACS Appl Mater Interfaces 8:24385–24393. CrossRefGoogle Scholar
  22. Matoussi N, Ameur HB, Amor SB, Fitouri Z, Becher SB (2007) [Cardiotoxicity of n-methyl-glucamine antimoniate (glucantime). A case report]. Med Mal Infect 37(Suppl 3):S257–S259. CrossRefGoogle Scholar
  23. Mayelifar K, Taheri AR, Rabaji O, Sazgarnia A (2015) Ultraviolet B efficacy in improving antieishmanial effects of silver nanoparticles. Iran J Basic Med Sci 18:677–683Google Scholar
  24. Messaritakis I, Mazeris A, Koutala E, Antoniou M (2010) Leishmania donovani s.l. Evaluation of the proliferation potential of promastigotes using CFSE staining and flow cytometry. Exp Parasitol 125:384–388. CrossRefGoogle Scholar
  25. Mlika BR, El Aïdli S, Ben Brahim M, Badri T, Chouk S, Ben Jannet S, Marrrak H, Daghfous R, Mokhtar I, Fenniche S (2008) [Adverse events related to systemic treatment using Glucantime for cutaneous leishmaniasis: a report from Tunisia]. Med Trop 68:499–501Google Scholar
  26. Natera S, Machuca C, Padrón-Nieves M, Romero A, Díaz E, Ponte-Sucre A (2007) Leishmania spp.: proficiency of drug-resistant parasites. Int J Antimicrob Agents 29:637–642. CrossRefGoogle Scholar
  27. Neouze MA, Schubert U (2008) Surface modification, functionalization of metal and metal oxide nanoparticles by organic ligands. Monatsh Chem 139:183–195. CrossRefGoogle Scholar
  28. Nilforoushzadeh MA, Shirani-Bidabadi L, Zolfaghari-Baghbaderani A, Jafari R, Heidari-Beni M, Siadat AH, Ghahraman-Tabrizi M (2012) Topical effectiveness of different concentrations of nanosilver solution on Leishmania major lesions in Balb/c mice. J Vector Borne Dis 49:249–253Google Scholar
  29. OPS/OMS (2017) Leishmaniasis. Informe epidemiológico de las Américas. Informe # 5. Organización Panamericana de la Salud y Organización Mundial de la Salud. Accesed 4 May 2017
  30. Oryan A, Akbari M (2016) Worldwide risk factors in leishmaniasis. Asian Pac J Trop Med 9:925–932. CrossRefGoogle Scholar
  31. Pourali P, Razavian Zadeh N, Yahyaei B (2016) Siler nanoparticles production by two soil isolated bacteria, Bacillus thuringiensis and Enterobacter cloacae, and assessment of their cytotoxicity and wound healing effect in rats. Wound Repair Regen 24:860–869. CrossRefGoogle Scholar
  32. Rai M, Yadav A, Gade A (2009) Silver nanoparticles as a new generation of antimicrobials. Biotechnol Adv 27:76–83. CrossRefGoogle Scholar
  33. Ravindran A, Chandran P, Khan S (2013) Biofunctionalized silver nanoparticles: advanced and prospects. Colloids Surf B 105:342–352. CrossRefGoogle Scholar
  34. Secretaría de Agricultura, Ganadería, Desarrollo Rural, Pesca y Alimentación (SAGARPA) (2001) NORMA Oficial Mexicana NOM-062-ZOO-1999 Especificaciones técnicas para la producción, cuidado y uso de los animales de laboratorio. Diario Oficial de la FederaciónGoogle Scholar
  35. Singh N, Kumar M, Singh RK (2012) Leishmaniasis: current status of available drugs and new potential drug targets. Asian Pac J Trop Med 5:485–497. CrossRefGoogle Scholar
  36. Wei Q, Ji J, Fu J, Shen J (2006) Norvancomycin-capped silver nanoparticles: synthesis and antibacterial activities against E. coli. Sci China Ser B 50:418–424. CrossRefGoogle Scholar
  37. Zhang XF, Liu ZG, Shen W, Gurunathan S (2016) Silver nanoparticles: synthesis, characterization, properties, applications, and therapeutic approaches. Int J Mol Sci. Google Scholar

Copyright information

© Springer Science+Business Media B.V., part of Springer Nature 2018

Authors and Affiliations

  1. 1.Centro de Investigaciones BiomédicasUniversidad Autónoma de CampecheSan Francisco de CampecheMexico
  2. 2.Departamento de Infectómica y Patogénesis MolecularCentro de Investigación y de Estudios Avanzados del Instituto Politécnico NacionalCiudad de MéxicoMexico
  3. 3.Departamento de Infectología e InmunologíaInstituto Nacional de PerinatologíaCiudad de MéxicoMexico

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