Contents lists available at ScienceDirect Photodiagnosis and Photodynamic Therapy journal homepage: www.elsevier.com/locate/pdpdt Hypericin-mediated photoinactivation of polymeric nanoparticles against Staphylococcus aureus Amanda Milene Malacrida a, *, Victor Hugo Cortez Dias a , Alex Fiori Silva a , Adriele Rodrigues dos Santos a , Gabriel Batista Cesar b , Evandro Bona c , Paula Aline Zanetti Campanerut-Sá a , Wilker Caetano b , Jane Martha Graton Mikcha a a Department of Clinical Analysis and Biomedicine, State University of Maringá, Maringá, Paraná, Brazil b Department of Chemistry, State University of Maringá, Maringá, Paraná, Brazil c Department of Food, Federal Technological University of Paraná, Campo Mourão, Paraná, Brazil ARTICLEINFO Keywords: Bioflm Foodborne diseases Hypericin Mathematical model Pluronic® P123 Photoinactivation Antimicrobial photodynamic therapy ABSTRACT Photoinactivation is a promising technique for Staphylococcus aureus control. This microorganism causes food- borne diseases (DTAs) and forms bioflms that are highly resistant and difcult to eradicate. Thus, the aim of this study was to evaluate the photodynamic activity of hypericin (HYP) in polymeric nanoparticles (Pluronic® P123) against S. aureus planktonic and bioflm cells. Planktonic cells and bioflms of S. aureus (ATCC 25923) were subjected to photoinactivation using low-power orange LED (0.3 mW/cm²) with diferent HYP formulation concentrations in Pluronic® P123. The P123 molar ratios were 2.5 (HYP/P123-2.5) and 10 (HYP/P123-10), respectively. The treatment times for planktonic cells were proposed by a mixture design, and bacterial pho- toinactivation was observed in concentrations of 12.5 to 3.12 μmol/L for HYP/P123-2.5 and reductions of ∼ 4.0 log CFU/mL in 12.5 to 0.78 μmol/L for HYP/P123-10. For bioflms, 30 min of darkness and 30 min of illumi- nation were used. Maximum reductions were similar for both formulations and corresponded to approximately 0.9 log CFU/cm². It was concluded that photoinactivation with longer lighting times was efective against planktonic cells and could be potentially applied to control S. aureus. 1. Introduction Photoinactivation is an efcient tool that has been used for micro- bial control in the medical [1], dental [2], industrial [3], and en- vironmental [4] felds, among others. With this technique, the photo- sensitizing (PS) molecule excitation with visible light results in the reactive oxygen species formation. This interacts with cellular structure components (nucleic acids, lipids, and proteins) and promotes cell death [5]. Nowadays, several compounds are recognized as PS, including hy- pericin (HYP). HYP is a naturally occurring highly lipophilic anthra- quinone that is extracted from Hypericum perforatum L. It is commonly known as St. John's Wort [6]. Several studies have shown HYP as a potent PS, exhibiting anticarcinogenic [7], antibacterial [7–9], anti- fungal [10,11], antiviral [12,13], and anti-bioflm actions [14–17]. However, the high lipophilic feature of HYP impairs its usage in aqu- eous solutions due to self-aggregate formations. In this sense, polymeric nanoparticles have been considered good vehicles for drug solubility [18–20] and photosensitizing agents [7,21], and they appear to be an efective solution against HYP self-aggregate formations in aqueous solutions [22]. Considering that HYP is a good PS, its application for controlling food-borne pathogens (such as S. aureus) has potential. S. aureus is a common pathogen associated with outbreaks of food poisoning [23] and can be found in several foods [24–26]. S. aureus forms bioflms on surfaces commonly found in food processing environments [27,28]. Due to its complexity, the bioflm structure is considered to be more resistant to antimicrobial agents than planktonic cells [29,30]. The control of S. aureus is imperative to ensure food safety and protect human health. Considering these elements, the aim of this study was to evaluate photodynamic activity of HYP in polymeric nanoparticles (Pluronic® P123) against planktonic cells and S. aureus bioflm. https://doi.org/10.1016/j.pdpdt.2020.101737 Received 11 December 2019; Received in revised form 19 February 2020; Accepted 9 March 2020 ⁎ Corresponding author at: Department of Clinical Analysis and Biomedicine, State University of Maringá, Av. Colombo 5790, Block T-20, CEP 87020-900, Maringá, Paraná, Brazil. E-mail addresses: amandamalacrida@gmail.com, pg54180@uem.br (A.M. Malacrida). Photodiagnosis and Photodynamic Therapy 30 (2020) 101737 Available online 19 March 2020 1572-1000/ © 2020 Elsevier B.V. All rights reserved. T