Previous studies showed that surface size, and not surface charge, plays a large role in the therapeutic effect of Au-NPs. Generally, Au-NPs for drug delivery and photothermal therapy applications have dimensions larger than 10 nm, which is sufficient to decrease the surface reactivity and thus make gold cores benign. A size larger than 6�C8 nm is also optimal for precluding renal excretion and consequently diminishing the circulatory half-life. Unexpectedly, our results showed that the proliferation of A549 cells was promoted after 24-h treatment with Au-NPs of 20 nm or 40 nm in diameter. This phenomenon was not observed in 95D cells. Moreover, 5-nm Au-NPs and 10- nm significantly promoted the invasion of A549 and 95D cells, respectively, while the invasive L-Quisqualic acid ability was not affected in the presence of particles with a size greater than 20 nm. These results support the view that Au-NPs do not universally target all cell types. Coulter et al. found that the surviving fraction for Au- NPs�Ctreated cells showed a strong dependence on the cell type MDL 100907 compared with that of untreated cells in respect to radiosensitization potential. In our study, the improved invasion ability was accompanied by a notable upregulation of ICAM-1 and MMP-9 expression. Invasion through the ECM is an important step in tumor metastasis. Cancer cells initiate invasion by adhering to and spreading along the blood vessel wall. Matrix metalloproteinases are endopeptidases that are able to degrade ECM components, which allows cancer cells to access the vasculature and lymphatic systems. MMP-9 has attracted much attention for its ability to degrade type IV collagen, the basic component of the basement membrane. Increased expression of MMP-9 in patients with non-small cell lung cancer has been reported ; therefore, agents suppressing the expression of the MMPs could inhibit cancer cell migration and invasion. ICAM-1 is a representative adhesion molecule involved in the interaction among tumor cells, the endothelium, and ECM. High expression of ICAM-1 in human lung cancer specimens was correlated with a greater risk of advanced cancers. A549/ICAM- 1 cells were shown to induce in vitro cell invasion and in vivo tumor metastasis. Denissenko et al. observed that ICAM-1 downregulation at the mRNA and protein levels led to strong suppression of human breast cell invasion through a Matrigel matrix. We found that 5-nm and 10-nm Au-NPs effectively promoted the expression of ICAM-1and MMP9 in A549 and 95D cells, respectively, which partially explained the enhanced action of the particles on cancer cell invasion. Since the upregulation effects of Au-NPs on MMP-9 and ICAM-1 expression in A549 and 95D cell suggested that small particles might possess the ability to facilitate the invasion of lung cancer cells, further in vivo studies are required to confirm the mechanisms.