Fig. 1: (A) Schematic diagram of protease-activatable gold-quenched imaging probe. (B) In vivo near-infrared optical imaging of protease (matrix metalloproteinases, MMPs) positive SCC7 xenografts after intratumoral injection of gold probes without (left) or with (right) MMPsinhibitor. (C) Fluorescence image from wells containing the probe in the presence of various concentrations of protease (MMPs) following incubation. (D) Fluorescence microscopy of tumors injected with the probe that were untreated (left) or treated (right) with inhibitor.

Nanotechnology offers exciting new techniques for detecting and tracking the proteins involved in cancer and other diseases. Kwangmeyung Kim at Korea Institute of Science and Technology, Cheol-Hee Ahn at Seoul National University and co-workers1 have developed tiny probes made from gold nanoparticles that show great potential for tracking important enzymes through the body.

In order to be effective for imaging, nano-sized probes must be able to absorb particular wavelengths of light, and have specific properties that are recognized by the molecules they are designed to image. Many such probes have been developed using tiny particles of semiconductors, magnetic materials and polymers, but it has proven difficult to provide enough absorbance for a high-resolution image.

Kim, Ahn and co-workers prepared new probes just 20 nanometres in size by coating gold nanoparticles with a fluorescent dye. They chose dye molecules containing a peptide chain that reacts with protease enzymes—important targets for drugs because they promote cancer, inflammation and vascular diseases.

The dye molecules usually fluoresce under near-infrared light, but in the new nano-probes their fluorescence is suppressed. This is because the gold nanoparticles attract electrons from parts of the dye molecules called the chromophores, which are responsible for color. However when the nano-probes reach an area of protease activity, the dye molecules are released by the gold nanoparticle, producing fluorescence that is easily visible with optical instruments.

The probes were tested by injecting them into mice with cancerous tumors that are promoted by specific proteases. The researchers observed a large increase in near-infrared fluorescence around the tumor site, providing clear visualization as early as 30 minutes after injection.

However, the probes only worked when they were injected directly into the tumor, and not when injected into the bloodstream, possibly because they were cleared out through the liver. The researchers hope to overcome this problem in the future by reducing the size of the probes.

The study presents a simple and inexpensive means of visually monitoring protease activity. This method could potentially be targeted to any protease by choosing an appropriate peptide when making the dye molecules.