We designed and synthesized novel and smart AuNPs (Au nanoparticles) capped MSNs (mesoporous silica nanoparticles) for lung caner cellular MR/optical multimodal imaging, as shown in Figure 1. MSNs were doped with FITC to enable the fluorescent imaging. The 19F MRI contrast agents were encapulated in the MSNs via capped AuNPs, which prevented the premature release of the contrast agents. AuNPs were covalently conjugated onto the MSNs by acid-cleavable hydrazone linkages, which were stable at neutral pH, but were cleaved at mildly acidic environment. Folate has been covalent conjugated on AuNPs via the formation of amide bonds for targeting the lung cancer cells, because folate-binding proteins (FBP) are selectively overexpressed on the cancer cell membranes. Figure 2 shows 19F NMR spectroscopy of AuNPs-MSNs after the intubation with PBS pH 7.4, PBS pH 6.0, normal cells (MRC-5) and lung cancer cells (A549). For the normal cells with neutral pH, the 19F MRI shows ‘dark’ as the 19F contrast agents are trapped in the AuNPs-MSNs (Figure 3). However, for the cancer cells with acidic pH, the folate-functional AuNPs-MSNs are able to enter the cancer cells. The hydrazone bonds are cleaved by the intracellular acidic environment (pH 5–6), resulting in ‘light on’ of the 19F intracellular MRI due to the release of 19F contrast agent from the MSNs (Figure 3). The optical imaging confirmed the above MRI results (no shown here for the limited space).