# Research Progress of Polysaccharide-Gold Nanocomplexes in Drug Delivery
## 4 Application of polysaccharide-AuNPs  
Polysaccharides have immunomodulatory functions; however, the efficacy of polysaccharides for cancer therapy remains poor. One possible reason is their low prescribed dose and rapid clearance in the clinical setting. One solution to this issue is combining polysaccharides with nanomaterials, which can enhance the immunostimulatory activity of polysaccharides and produce a more substantial tumor therapy effect. In particular, preparing AuNPs using plant extracts offers several advantages over synthetic approaches. This method provides a more accessible and cheaper route to industrial scale-up and has a higher safety profile for humans [87]. The chemical groups present in polysaccharides give them the ability to act as reducing or stabilizing agents in preparing AuNPs. The mechanisms involved in synthesizing AuNPs from polysaccharides can be classified into three categories, depending on the specific type of polysaccharides and the reaction conditions. These categories include glycosidic bond breaking, hydroxyl group reduction, and amino group reduction (Figure 5) [88]. [PERSON] et al. conducted a study in which they synergistically combined immunologically active Ganoderma lucidum polysaccharides with gold nanomaterials. This combination proved effective in inducing the maturation of DCs, stimulating the proliferation of CD4+ and CD8+ T cells, and inhibiting the growth and metastasis of tumor cells. Notably, the researchers discovered that the addition of doxorubicin to the combined treatment further enhanced its effectiveness in treating tumors, and the combination of polysaccharides and nanomaterials can achieve the same therapeutic effect while reducing the dose of chemotherapeutic drugs and polysaccharides [89]. Polysaccharides can be utilized as reducing and stabilizing agents to synthesize polysaccharide-AuNPs, which can efficiently safeguard orally administered insulin from degradation. This is because polysaccharides remain undigested in the gastrointestinal tract, making them suitable for treating diabetes mellitus. [PERSON] et al. confirmed the above using apple polysaccharide-AuNPs, but the mechanism and pharmacokinetics still need further study [90]. Polysaccharides alone and AuNPs alone have limitations in disease treatment. However, when polysaccharides are combined with AuNPs, the resulting polysaccharide-AuNPs can offer a more promising approach. By combining the targeting ability of gold nanoparticles with the biological activity of polysaccharides, polysaccharide-AuNPs exhibit enhanced antitumor, immunocompetent, and antiviral effects. They also possess the targeting, photothermal effects, and carrier effects of AuNPs. As a result, the synergistic integration of both components allows polysaccharide-AuNPs to better fulfill their role in disease treatment. The mechanisms of preparation of polysaccharide-based AuNPs is categorized into three types: glycosidic bond disruption via Au(III) or base-mediated generation of highly reduced intermediates, reduction of free hydroxyl groups, and reduction of free amino groups. Polysaccharides are degraded under base-mediated conditions to intermediatescontaining aldehydes or \(\alpha\)-hydroxyketones, which are subsequently oxidized to carboxylation by-products to maintain the stability of AuNPs (Figure 5A). The Au (III) ion promotes intramolecular or intermolecular nucleophilic attack, leading to the protonation of the oxygen atom on the glycoside, triggering a break in the glycosidic bond. The O-5 and C-1 bonds within the inner ring then undergo heterogeneous decomposition, exposing highly reduced free aldehyde or ketone groups that facilitate the Au (III) ion to Au (0) atoms (Figure 5B). The seed growth process begins by nucleating seed particles (b) through the rapid reduction of the gold halide salt (a). These seed particles then serve as non-homogeneous nucleation sites in a subsequent reaction, leading to the controlled growth of particles with a well-defined shape (c) (Figure 5C).