A gold nanocage and dye conjugate has been demonstrated for use with photoacoustic imaging and fluorescence detection of protease activity. The detection sensitivity could be maximized by using gold nanocages with a localized surface plasmon resonance peak away from the emission peak of the dye. These hybrids can be potentially used as multimodal contrast agents for molecular imaging. ; NIH[DP1 OD000798, P30 CA91842]; NCI[R01 CA13852701]; Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital; Washington University School of Medicine; China Scholarship Council; NSF[ECS-0335765]