Hollow gold nanospheres (HGN) may be delicately tuned to absorb near infrared light (NIR) by tailoring the diameter-to-shell ratio. This unique property can be utilized for enhancing the contrast for the NIR and X-ray/CT imaging, and also noninvasive and local, photothermal hyperthermia by conjugating cancer-targeting molecules on the particle surface. In addition, when an NIR fluorophore is placed on the surface of the NIR-tuned HGNs, the fluorescence can be significantly quenched due to the emitted light absorption by the HGNs. Combining the NIR fluorescence quenching property of HGNs and the enzyme secreting nature of cancer, we have developed a novel enzyme-triggered NIR contrast agent for cancer detection with high specificity. NIR fluorophore Cypate (Indocyanine Green based) was conjugated to HGN via a short spacer for fluorescence quenching. The spacer contains an enzyme-substrate-motif (G-G-R) that can be cleaved by urokinase-type plasminogen activator (uPA, a breast cancer enzyme). The nano-complex normally does not emit fluorescence but, in the presence of uPA, the fluorescence was restored, providing high specificity. The enzyme-specific emission allows us to characterize the nature of the cancer (e.g., invasive, metastatic, etc.). Once the cancer is detected, the same HGNs can be used to deliver heat to the cancer site for cancer-specific hyperthermia.