In living organisms, the production and scavenging of reactive oxygen species (ROS) are strongly controlled by the antioxidant defense system. ROS are highly reactive oxygen derivatives and mainly include superoxide (O2•−), hydroxyl radicals, hydrogen peroxide (H2O2), and hypochlorite [1]. These species are generally regulated in an equilibrium state to protect the body from invading pathogens and are involved in physiological processes, such as wound healing and tissue repair [2,3]. However, abnormal overexpression of ROS causes oxidative stress, leading to tissue degeneration and various human diseases [4,5,6]. Researchers have developed several antioxidant nanoparticles (NPs) that control oxidative stress by acting through chemical mechanisms analogous to in vivo redox reactions. For example, cerium NPs mimic antioxidant enzymes such as superoxide dismutase and catalase. Cerium can transfer O2•− to H2O2 by exchanging its transition states [7]. Similarly, selenium and vanadium NPs are potent antioxidant materials because of their glutathione-peroxidase-mimic capacity [8]. Recently, Zhang et al. reported the peroxidase-, catalase-, and superoxide-dismutase-like activities of Prussian blue (PB) NP [9], a mixed-valent iron cyanide complex, Fe4III[FeII(CN)6]3, that exists in two transition states and shows strong antioxidant activity [10]. Thus, it exerts therapeutic effects on inflammatory diseases, such as colitis and ischemic stroke, by regulating ROS levels [11,12]. Although further study is required to clarify the exact mechanism of PB’s anti-inflammatory activity, the antioxidant and anti-inflammatory effects of PB have been found to be beneficial for cutaneous wound healing [13]. There have been several reports about the wound-healing efficacy of antioxidant and anti-inflammatory materials. Considering that an excessive ROS level interrupts the healing process, it was reported that redox homeostasis is essential in wound healing [14]. Overproduction of NO results in cytotoxicity and inflammation as an important inflammatory agent. Luo et al. reported that acute inflammation inhibits M1-to-M2 macrophage polarization for tissue regeneration and differentiation [15]. Thus, overexpressed NO inhibitor or scavenger promotes cell migration and proliferation.PB NPs have been traditionally used as dyes [16] as well as in electrochromic devices [17,18,19] and biosensors [20,21] because of their characteristic blue color and unique electrochemical properties [22]. These NPs have also been approved by the U.S. FDA and have gained attention in the biomedical field as biocompatible antidotes for radioactive thallium and cesium [23]. Although PB NPs are widely used in biomedical fields, their application remains challenging because of their instability in biological buffers and long-term aqueous solutions [24]. Thus, several polymers have been used as stabilizing agents to improve the stability of PB NPs, such as poly(vinylpyrrolidone), chitosan, and polyethylene glycol [25,26,27]. The stabilizing agents are important for preparing highly dispersible PB NPs. Furthermore, they can control the growth of PB NPs with unique size- and shape-dependent properties.Pluronic may be an excellent candidate as a stabilizing agent for PB NPs. This biocompatible copolymer is composed of one poly(propylene oxide) or two poly(ethylene oxide) blocks [28]. More than 50 types of Pluronic are commercially available, and their properties can be determined based on their block lengths and molecular weights [29]. Pluronic series are characterized by their hydrophilic–lipophilic balance (HLB) value, which is a fractional ratio of the lipophilic region to the hydrophilic region of an amphiphilic molecule. This value is critical to stabilize and optimize the characteristics of metal nanoparticles [30,31]. However, to the best of our knowledge, Pluronic series have not been used as stabilizing materials to improve and optimize the stability of PB NPs.

In this study, we developed Pluronic-stabilized PB NPs (PB/Plu NPs) with easy size control, as well as improved stability and efficacy, by using different types of Pluronic (F68, F127, L35, P123, and L81) as templates, and the resulting PB/Plu NPs were denoted by the type of Pluronic series (e.g., PB/PF68 NP for PB NPs developed with Pluronic F68). The physicochemical characteristics of PB/Plu NPs with different HLB values of the Pluronic triblock copolymers were analyzed, and the influence of templating materials on the antioxidant activity of PB/Plu NPs was assessed both in situ and in vitro. The migration and proliferation of fibroblasts via ROS scavenging and anti-inflammation were also evaluated.