AgNPs play a significant role in nanotechnology and nanoscience, particularly in nanomedicine [1]. In recent years, AgNPs have been shown several applications, where various of their applications depend on their size, shape, and dielectric environment [2, 3]. Although numerous noble metals have been used for different purposes, AgNPs have been focused on potential applications in cancer therapy [1], diagnostic, and therapeutic applications in medicine [2]. For example, AgNPs are being used as successful qualified antimicrobial agents around the world and have shown an important antimicrobial activity [2].
In addition, the antimicrobial properties of AgNPs apply to a significant target in enhancing the activity of drugs such as Amphotericin B, Nystatin, and Fluconazole, and composite scaffolds in order to control drug release and targeted drug delivery as a result of their biocompatibility and low toxicity [3]. Different applications require the preparation of AgNPs with good stability. For this reason, the green synthesis of stable silver nanoparticles (AgNPs) using vitamin C and kojic acid as stabilized ligands are used in this study. In addition, it is essential to find non-toxic, and natural products for functionalizing metal NPs in an aqueous medium [4]. For instance, the VC is a biomolecule readily available in nature and was used as a stabilized ligand for SnO2 NPs. It showed an advantageous effect on the body weight of neonatal rats, as mentioned in the literature [4]. VC is used with SnO2 NPs as both a reducing and capping agent through the synthesis of SnO2 NPs [4]. Herein, NaBH4 was employed as a reducing agent to produce AgNPs with small sizes and good long-term stability.
It is worth mentioning that in the early 1970s, the two-time Nobel Prize-winning chemist Linus Pauling reported that vitamin C in high doses reduced cancer by acting as an antioxidant [5]. Also, it is demonstrated that intravenous administration of vitamin C, followed by oral use, increases the survival rate of cancer patients. [7–8]. Conversely, other clinical studies have shown that vitamin C offers a low antitumor effect [5, 9, 10]. From our perspective, combining vitamin C with AgNPs could increase its efficacy.
It is known that VC has been shown to inhibit the production of free radicals and reduce oxidative stress caused by reactive oxygen species (ROS). Since many chronic diseases including cancer, diabetes, inflammation, atherosclerosis, neurodegenerative diseases, and aging are linked with oxidative stress [5], it has also been found that ROS can lead to cell death, because several cancer cells have lower levels of antioxidant enzymes in comparison with normal cells [5].
The properties of vitamin C may have dramatically changed when it is used as a functionalized ligand for nanomaterials, such as being more effective compared to vitamin C alone [4]. In the future, a lower vitamin C dose might be more beneficial against numerous diseases due to the promising outcomes of vitamin C-stabilized AgNPs.
The second ligand used in this work is kojic acid which is also considered an antioxidant agent [11]. Kojic acid has two different hydroxyl groups, and its chemical structure is (5-hydroxy-2-(hydroxymethyl)-4H-pyran-4-one) as shown in Scheme 1. It possesses antioxidant activity and protects the skin from harmful UV radiation and sunlight by scavenging free radicals that are generated by the reactive oxygen species [12]. Moreover, it is also considered to be one of the main drugs used in the treatment of skin whitening, anti-browning, and antibacterial agents [13, 14]. In addition, KA is widely used as a food additive to reduce food browning [15]. In Japan, for example, KA is used in the production of traditional foods such as sake, shoyu, and mirin, where it is also used as a food preservative [16]. Furthermore, the Food and Drug Administration (FDA, USA) approved the use of KA associated with other compounds for dermatological treatment purposes [16].
The silica nanoparticle was used as a drug delivery system after being functionalized by kojic acid, due to its interesting characteristics such as large surface area, high volume, and good biocompatibility [13]. On the one hand, KA solid lipid nanoparticles (KA-SLNs) were produced and showed that KA-SLNs dispersion enhanced percutaneous delivery of KA as a promising and potential novel topical preparation which might open new paths for the treatment of hyperpigmentation disorders [17]. According to Wu, Y., et al, [18] KA has antibacterial properties against gram-negative bacteria, due to the presence of the free CH2OH group at C-2 [18]. Kojic acid could offer more effective if linked with NPs. Biocompatible AgNPs with these stabilized ligands offered high stability and could be stored for a long time at normal conditions in this study.