Contents lists available at ScienceDirect Experimental Parasitology journal homepage: www.elsevier.com/locate/yexpr Biogenic silver nanoparticles reduce adherence, infection, and proliferation of toxoplasma gondii RH strain in HeLa cells without inflammatory mediators induction Laís Fernanda Machado a , Raquel Arruda Sanfelice a , Larissa Rodrigues Bosqui a , João Paulo Assolini a , Sara Scandorieiro b , Italmar Teodorico Navarro c , Allan Henrique Depieri Cataneo d , Pryscilla Fanini Wowk d , Gerson Nakazato b , Juliano Bordignon d , Wander Rogerio Pavanelli a , Ivete Conchon-Costa a , Idessania Nazareth Costa a,∗ a Departamento de Patologia Experimental – Laboratório de Imunoparasitologia Das Doenças Negligenciadas e Câncer. Universidade Estadual de Londrina, 86057-970, Londrina, Paraná, Brazil b Departamento de Microbiologia – Laboratório de Bacteriologia Básica e Aplicada. Universidade Estadual de Londrina, Paraná, Brazil c Departamento de Medicina Veterinária Preventiva – Laboratório de Zoonoses e Saúde Pública. Universidade Estadual de Londrina, PR, Brazil d Laboratório de Virologia Molecular. Instituto Carlos Chagas, ICC/ Fiocruz, Curitiba, Paraná, Brazil ARTICLE INFO Keywords: Silver nanoparticles Treatment Toxoplasmosis HeLa cells ABSTRACT The highlights of biogenic silver nanoparticles (AgNp-Bio) include low toxicity – depending on size and con- centration – and efficient antiparasitic activity. Therefore, the objective of this study was to assess the action of the AgNp-Bio on HeLa cells in an infection with strain of RH Toxoplasma gondii. Firstly, we performed a cellular viability test and characterized the AgNp-Bio to proceed with the infection of HeLa cells with T. gondii to be treated using AgNp-Bio or conventional drugs. Subsequently, we determined the level of standard cytokines Th1/Th2 as well as the content of nitric oxide (NO) and reactive oxygen species (ROS). Results indicated a mean size of 69 nm in diameter for the AgNp-Bio and obtained a dose-dependent toxicity. In addition, the con- centrations of 3 and 6 μM promoted a significant decrease in adherence, infection, and intracellular prolifera- tion. We also found lower IL-8 and production of inflammatory mediators. Thus, the nanoparticles reduced the adherence, infection, and proliferation of ROS and NO, in addition to immunomodulating the IL-8. Therefore, our data proved relevant to introduce a promising therapeutic alternative to toxoplasmosis. 1. Introduction Toxoplasmosis is an infection caused by the compulsory in- tracellular protozoan Toxoplasma gondii and represents a public health issue that affects around 30% to 50% of the world population (Montazeri et al., 2017). In 90% of the causes, the infection develops without symptoms or is benign (Robert-Gangneux and Dardé, 2012; Krueger et al., 2014). However, it is possible for immunocompromised individuals to develop a severe clinical condition (Sutterland et al., 2015; Atilla et al., 2015; Alday et al., 2017). The organism does not tolerate well the association of pyrimethamine and sulfadiazine used to treat symptomatic cases, which interact indistinctly with biochemical processes of both the parasite and the host (Sepúlveda-Arias et al., 2014) generating adverse effects, such as the suppression of bone marrow, which may lead to megaloblastic anemia, leukopenia, and granulocytopenia (Petersen, 2007). In this context, investment has focused on the study of nanoma- terial, whose actions involve carrying drugs, decreasing toxicity, mod- ulating pharmacokinetics, and increasing bioavailability, in addition to releasing the drug directly into the specific target (Khalil et al., 2013; Torres-Sangiao et al., 2016). Silver nanoparticles (AgNp) are commonly used for a variety of medical applications, especially for their anti-in- flammatory and antimicrobial activities (Pourali and Yahyaei, 2016) (Shrivastava et al., 2007; Adair et al., 2010; Scandorieiro et al., 2016) found in Gram-positive and Gram-negative bacteria (Shrivastava et al., 2007; Scandorieiro et al., 2016; Durán et al., 2016), filamentous fungi (Sanguiñedo et al., 2018), some types of viruses (Park et al., 2018; Sharma et al., 2019), and protozoa of the genus Leishmania https://doi.org/10.1016/j.exppara.2020.107853 Received 24 October 2019; Received in revised form 17 January 2020; Accepted 8 February 2020 ∗ Corresponding author. ,. Department of Pathological Sciences Center of Biological Sciences State University of Londrina, CEP, 86057-970, Londrina, PR, Brazil. E-mail address: idessania@uel.br (I.N. Costa). Experimental Parasitology 211 (2020) 107853 Available online 12 February 2020 0014-4894/ © 2020 Published by Elsevier Inc. T