# Gold Nanoparticles for Drug Delivery and Cancer Therapy
## 3 Cellular Uptake of Gold Nanoparticles and Cytotoxicity
It was reported that small Au NPs (4-5 nm) have higher toxicity potential than large particles (18-20 nm) [49], and the size-dependent interaction between sub-nanometer Au NPs and the glycocalyx is relevant to the cellular uptake [50]. Research showed that Polyethylene Glycol-coated Au NPs had a transfection efficiency and cell uptake greater than 45% in each case with low cellular toxicity, and can be used as a DNA and drug delivery system reliably [51]. PEG is a common coating material used on Au NPs to reduce NP interaction with biological specimens. Research was carried out to investigate the effect of PEG on cellular uptake on three types of cells. The study also checked for the oxidative stress, cell morphology, and functionality. The result shows that PEG affects the cellular uptake of NP in a cell-dependent manner and influences toxicity by different mechanisms [52]. For in vivo toxicity, [PERSON] et al [53] found that the 13 nm PEG-coated Au NPs induced acute inflammation and apoptosis in the human liver. Moreover, [PERSON] et al [54] carried out biokinetics studies on PEG-modified Au NPs. They found that after intravenous injection, a prolonged blood circulation time was found for the PEG-modified Au NPs, which mostly accumulated in the liver and spleen. Multi drug resistance (MDR) has great influence on the success rate of cancer chemotherapy. A membrane-bound active drug efflux pump is a transporter that can efflux a wide range of anticancer agents. It is the most important mechanism involving MDR, and P-glycoprotein (P-gp). Most anticancer agents are stopped at the plasma membrane, where more inhibition or bypass of P-gp mediated drug efflux is important in MDR and drug delivery to the target cell. Au NPs are good quenchers for fluorescence donors due to the effect of surface energy transfer. This specific property allows Au NPs to become the base of the fluorescent nanoprobe. A drug system was developed, where doxorubicin was tethered onto the surface of Au NP with PEG through an acid labile linkage. This Au NP complex significantly overcame the P-gp mediated drug resistance due to the enhanced release of doxorubicin cellular entry and doxorubicin in acidic organelles. The intracellular responsive release was monitored by the recovery of fluorescence signals quenched by the Au NPs [55]. The cellular uptake of Au NPs is often dependent on the target molecule, and it can have a big impact on the treatment outcome. A study was carried out where the systematic delivery of siRNA to solid tumor in cervical cancer was investigated using unimer polyion complex Au NP, and targeting ligand cyclic Arg-Gly-Asp specifically binds to \(\alpha\)v\(\beta\)3/\(\alpha\)v\(\beta\)5 integrins, which are overexpressed in cancer cells. The in vivo result shows that the targeting ligand has higher uptake by the cancer HeLa cells and shows significantly enhanced gene silencing [56]. Genotoxicity, cytotoxicity and the apoptotic effect of Au NPs were observed in normal liver cells and cancer liver cells. Green Au NPs caused intracellular reactive oxygen species, reduced total glutathione, and mitochondrial membrane potential in both the cells in a dose dependent manner. N-acetyl-L-cyteline inhibits the generation of reactive oxygen species in both cells after exposure. Maximum DNA damage was observed at 700 mg/ml green Au NPs after 1 day of exposure. Healthy cells are more sensitive to green Au NPs than liver cancer cells. In both cells, cytotoxicity and apoptosis are mediated through the oxidative stress [57]. In the liquid phase, electrical discharge plasma causes reactive species leading to rapid reactions such as the degradation of biopolymers. In a plasma treatment study, N,O carboxymethylchitosan-stabilized Au NP was used to cause plasma-induced degradation, which leads to a decrease in the hydrodynamic diameter of carboxymethyl chitosan Au NPs from 400 nm to 100 nm. It also results in a narrow NP size distribution with diameter ranging from 2 nm to 40 nm.