Nanomaterials with various shapes and sizes are currently being used in the biomedical field, such as liposomes, carbon quantum dots, and metal nanoparticles [[1], [2], [3]]. Among them, gold nanoparticles (Au NPs) show great potential applications in the delivery of pharmaceutical actives, bioimaging, and biosensing due to ease of synthesis and surface modification, unique physical properties, and excellent biocompatibility [[4], [5], [6]]. However, most Au NPs were produced using traditional chemical synthesis methods involving toxic and hazardous chemicals (e.g., CTAB and triphenylphosphonium) as ligands, significantly harmful to organisms and the environment [7,8]. Furthermore, the instability of Au NPs, typical citrate-capped Au NPs, in physiological environments (e.g., salt ion concentration and type, pH, and biomolecules) further hinders their biomedical applications [6,9,10].

In recent years, polysaccharides have become a promising choice for preparing Au NPs because of their extensive sources, good biodegradability, and biocompatibility [[11], [12], [13]]. According to the type of polysaccharide and reaction conditions, the mechanism of action for prepared Au NPs from polysaccharides was divided into three main categories: glycosidic bond breaking to produce highly reducing intermediates (exposing free aldehyde or ketone groups), reduction of hydroxyl groups, and reduction of amino groups [14]. Under base-mediated conditions, certain polysaccharides (e.g., pullulan and starch) induce glycosidic bond breakage, producing short-chain fragments with high reductivity [15,16]. This results in Au (III) being reduced to Au (0) crystal species, which grow further into Au NPs. On the other hand, polysaccharides (e.g., cellulose nanocrystals and Lentinan) rich in hydroxyl groups could be used as templates for the alignment of Au NPs, and the FTIR confirms that -OH was involved in the reduction of gold precursors [17,18]. More importantly, the oxidation of -OH occurs only in the more reactive primary hydroxyl groups, while the secondary hydroxyl groups are not oxidized. Furthermore, chitosan with amino groups was also used for preparing Au NPs. When the environment was slightly acidic, -NH2 protonated to form -NH3+, leading to electrostatic adsorption of the AuCl4− ion onto the molecular chain. Then, Au (III) was reduced to Au (0) via free -NH2 [19,20]. Nevertheless, natural active polysaccharides' structural complexity (e.g., molecular weight, monosaccharide composition, degree of branching, substituent groups) leads to variations in the reaction conditions and reaction mechanisms for preparing Au NPs. More importantly, natural active polysaccharides possess excellent bioactivities, which could endow Au NPs with new functional activities (e.g., antioxidant, antitumor, immunomodulatory) [[21], [22], [23], [24]]. However, the current preparation of polysaccharide-Au NPs usually requires harsh reaction conditions (e.g., alkaline or boil) [15,18,25,26], which may destroy the structure and activity of the polysaccharides. Therefore, it is necessary to further develop methods for preparing highly stable and biologically active Au NPs under mild conditions using naturally active polysaccharides.

In this study, three natural active polysaccharides (Ganoderma lucidum polysaccharides (GLP), Lycium barbarum polysaccharides (LBP), and Astragalus polysaccharides (ASP)) were used as reducing and stabilizing agents, and highly stable Au NPs were successfully synthesized by mixing them directly with the gold precursors without additional reagents. Then, the effects of the synthesis conditions were investigated, and the possible synthesis mechanism was proposed: HAuCl4-mediated glycosidic bond breaking to expose a highly reducing free aldehyde/ketone group, which reduced Au (III) to Au (0). Besides, the polysaccharide-Au NPs exhibit excellent stability in various physiological environments. More interestingly, polysaccharide-Au NPs retained the antioxidant properties of polysaccharides. This will provide new information for Au NPs applying in the biomedical field.