# Research Progress of Polysaccharide-Gold Nanocomplexes in Drug Delivery
## 5 Research on polysaccharide-AuNPs as Drug Delivery Carriers
There are two main ways to bind AuNPs to nucleic acids: (1) using cation-modified gold nanoparticles to bind nucleic acids to gold nanoparticles by electrostatic adsorption. (2) Modification of nucleic acids. Combining nucleic acids and AuNPs using a layer-by-layer deposition method provides a strategy for the controlled release of nucleic acids. Layer-by-layer coating of thioglycolic undecanoic acid-stabilized AuNPs with positively charged PEI and negatively charged siRNA layers yielded much higher cellular uptake of both siRNA/PEI-AuNPs and PEI/siRNA/PEI-AuNPs than that of citrate-stabilized AuNPs (Figure 6C) [123]. DNA was thiolated (-SH) and self-assembled using Au-S bonds to obtain DNA covalently bound functionalized AuNPs [124]. AuNPs have been utilized as carriers for nucleic acid delivery for several years. Initially, this was achieved through electrostatic adsorption of PEI. Subsequently, thiol-capped siRNAs were chemisorbed on the AuNPs [125]. However, research on polysaccharide-AuNPs for nucleic acid drug delivery in oligonucleotides and siRNAs is promising. SiRNAs are an immensely potent therapeutic tool due to their straightforward working mechanisms. They determine target genes by recognizing specific sequences and subsequently regulate their expression. However, the efficient delivery of siRNAs to the target organ has perpetually posed a daunting challenge that demands a solution [126]. Figure 6: (**A**): PEG-modified gold nanoparticles used to deliver DOX. Reproduced with permission from Ref. [127]. (**B**): Schematic representation of AuNPs-PEI-pDNA complexes entering and expressing in cells. Reproduced with permission from Ref. [128]. (**C**): Positively charged PEIs and coated mercaptoundecanoic acid MUA-stabilized AuNPs delivering siRNAs. Reproduced with permission from Ref. [123]. The positively charged AuNPs-PEI-pDNA complex can be attached to the cell periphery by electrostatic adsorption and enter the cell wall through the pores. Subsequently, it enters the cytoplasm through endocytosis at the cell membrane and further enters the nucleus. Due to the proton sponge effect of PEI, AuNPs-PEIs release the pDNA they carry to express the corresponding proteins through transcription and translation (Figure 6B) [128]. Au- and PEI-based couplers, modified with HA and DOX, deliver siRNAs while protecting against degradation and promoting their escape from endosomes. This enables a selective treatment for cancers [129]. [PERSON] et al. developed a nanosystem using HA-AuNRs, to which siRNA against B7-H3 (B7-H3 si) and glucose oxidase (GOx) were attached. This nanoplatform was designed for efficient low-temperature PTT. The study aimed to inhibit tumor cell proliferation, induce cell apoptosis and achieve effective tumor ablation under mild, low-temperature conditions (42-45 \({}^{\circ}\)C) while utilizing RNA interference [130]. The surface modification of AuNPs with HA and low molecular weight PEI enables the efficient transport of siRNA. This modified system serves multiple purposes, including gene silencing, photothermal therapy, and chemotherapy, which are vital in breast cancer treatment [129]. AuNPs can generate localized heat and deliver drugs near cancerous tissues. DOX, commonly used in clinical and research settings as an antitumor drug, has been the subject of numerous studies investigating the impact of polysaccharide-AuNPs on its delivery. [PERSON], [PERSON] et al. further stabilized AuNPs with mercapturized poly(ethylene glycol) and then covalently coupled them with poly(amidoamine) G4 dendrimers for efficient and specific delivery of doxorubicin. The gold nanocarriers prepared by this modification method have better colloidal stability and biocompatibility, and at the same time, they can be used as pH-triggered multifunctional nanopatforms (Figure 6A) [127]. These studies aim to explore the potential of polysaccharide-AuNPs in tumor treatment. A survey by [PERSON] et al. focused on synthesizing AuNPs using ticoadian to deliver the anticancer drug DOX.