# Enhanced Radiation Therapy of Gold Nanoparticles in Liver Cancer
###### Abstract  
Gold nanoparticles (GNPs) were widely used in X-ray imaging and radiation therapy due to strong photoelectric effects and secondary electrons under high energy irradiation. As liver cancer is one of the most common forms of cancer, the use of GNPs could enhance liver cancer radiotherapy. We synthesized polyethylene glycol (PEG)-coated GNPs of two different sizes by chemical reduction reaction. Blood stability, cellular uptake, cytotoxicity and radiation therapy were investigated. A 3-5 nm red shift of SPR caused by interactions between PEG-coated GNPs and plasma indicated their good stability. Cellular uptake assay showed that PEG-coated GNPs would enhance an appreciable uptake. GNPs preferred to combine with blood proteins, and thus induced the formation of 30-50 nm Au-protein corona. GNPs were endocytosed by cytoplasmic vesicles, localized in intracellular region, and presented concentration dependent cell viability. Clonogenic assay illustrated that the PEG-coated GNPs could sensitize two liver cancer cell lines to irradiation.  
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with hexadecyl-trimethyl-ammonium bromide were not biocompatible [36]. Besides, the size of GNPs also played an important role in the process of cellular uptake. For instance, 50 nm bare GNPs were found to have highest capability of cellular uptake [37; 38; 39], however PEG-coated GNPs of 10-30 nm exhibited a higher inducible effect in uptake [40; 41; 42; 43; 44; 45].  
Liver cancer (also named as hepatocellular carcinoma) is a common cancer [46] but with a very high fatality rate, almost all patients are dead within a year. The reason of high mortal rate was attributable to hepatitis virus infection. It was reported that about three quarters of patients suffering from liver cancer were found in Southeast Asia including China, Hong Kong, Taiwan, Korea and Japan. Unfortunately, the number of diagnosed patients in the whole world was increasing dramatically, and it will continue to go up over the next few decades. However, liver cancer cells were not sensitive to radiation, and no effective radio-sensitizer has yet been developed for therapeutic treatment. Thus it is really critical to develop an effective and safe method for hepatocellular carcinoma radiation therapy.  
In previous work, we investigated the in vivo toxicity and biological applications of GNPs and MoS2 dots in detail [6; 30; 47; 48; 49; 50; 51]. In this study, we will present the therapeutic effect of PEG-coated GNPs using human HepG2 and mouse H22 hepatocellular carcinoma cell line. We found that GNPs had a tendency to aggregate after adding a high concentration of salts and certain biological molecules including nucleic acids and some proteins. Stability of bio-conjugates of GNPs in aqueous solutions is a critical issue in bio-applications. In our study, we found PEG-SH modified GNPs to be more stable compared to other thiol-compounds in aqueous solutions (e.g., cysteine and homocysteine) [52]. We assessed the stability of GNPs in plasma, cellular uptake and their intracellular distribution, cytotoxicity, and radiation therapeutic effect under radiation by \({}^{137}\)Cs at doses of 0-4 Gy in two different cell lines. It was illustrated that modifying the surface coating of nanoparticles could achieve low cytotoxicity and high radio-sensitization effect in liver cancer therapy.