# Gold Nanoparticles for Drug Delivery and Cancer Therapy
## 4 Gold Nanoparticle-Based Drug Delivery
### Small Interfering Ribonucleic Acids (siRNAAs) Delivery  
Small interfering ribonucleic acids have vast therapeutic potential, therefore they opened up a lot of novel clinical research areas focusing on numerous applications [90]. For effective cancer treatment, small RNA interference is a promising strategy. However, it has some major complications--such as easy degradation of small interfering RNA. For the treatment to be viable, siRNA delivery requires a vector system that has excellent biocompatibility, specific target property and efficient transfection efficiency. For the case of delivering siRNA to glioblastoma cells, a PEI entrapped Au NP modified with arginine-glycine-aspartic (Arg-GLY-Asp, RGD) peptide through a PEG spacer as a vector for B-cell lymphoma-2 (Bcl-s) was used, and the effect was observed. The Au NPs were used to deliver enhanced green fluorescent protein (EGFP) reporter genes. This gene expression demonstrated the highest mean fluorescence at an N/P ratio of ten. The siRNA delivery was checked using the flow cytometry, protein expression level analysis, and confocal microscopic imaging. The outcome of the flow cytometry and confocal microscopic image were consistent with pDNA transfection performance,and the experimental results show that the siRNA-encapsulated Au NPs could deliver Bcl-2 siRNA to U87 MG cells with good transfection efficiency, and were capable of specific gene silencing in the target cells using an RGD peptide-mediated pathway [91]. Prostate cancer is one of the leading causes of cancer related death in men, especially in patients who have developed metastatic castrate resistant disease with very limited therapeutic options available to them. Recent research shows that using siRNA to silence some genes has high potential in this treatment. However, there is a major barrier that needs to be dealt with. When using siRNA in therapy, the siRNA duplexes are very unstable and have very low cellular uptake efficiencies. These may induce immune system activation. Furthermore, without a target ligand, any cell within the body can be transfected, and this can cause serious harm and health consequences to healthy cells and body. Au NPs can overcome most of these barriers and can protect the siRNA from enzymatic degradation and mediate gene silencing. A study was conducted where Au NPs were coated with PEI and conjugated with targeting ligand anisamide that is bound to the sigma receptor overexpressed on the surface of prostate cancer cells. These Au NPs encapsulate the siRNA and uptake into PC3 prostate cancer cells. It resulted in the highly efficient knockdown of the ReIA gene. The result shows that it is a viable option for therapeutic use [92]. Melanoma has a very high mortality rate and is related to the proliferation of pigment-producing melanocytes in epidermis. It is normally treated with surgical restriction and chemotherapy. Study shows that these cancer cells start to demonstrate resistance to the chemotherapeutic agents. Signal transduction and activator of transcription factor 3 (STAT3) seem to be constitutively active in most melanomas, and need to be targeted for tumor control. There is no clinically approved small molecule inhibitor of STAT3, but siRNA can be used to silence the gene. A therapeutic system where the co-delivery of anti-STAT3 siRNA, and imatinib mesylate encapsulated in Au NPs was proposed to silence the gene. Experimental results using this method showed a significant reduction in percentage tumor volume (\(p<0.05\)), and weight [93]. On the other hand, breast cancer is one of the most common cancers in women and has a high risk of tumor recurrence and metastasis. The cancer stem-like cells (CSCs) are highly involved in drug resistance, metastasis, and relapse of the tumor due to their self-renewal ability and multilineage differentiation capacity. siRNA can be used in the sequence-specific silencing of RNA-coding cancer-related proteins in cells.