In order to efficiently utilize nanoparticles in imaging and diagnostic applications, it is critical to distinguish particles that have been internalized by their cellular target from those that have not. The ability to differentiate between the two is essential for quantification and visualization, as well as determining the efficiency of drug delivery protocols.
Etchable plasmonic nanoparticles
Led by Erkki Ruoslahti, a professor at the University of California Santa Barbara (UCSB), researchers have harnessed the inherent plasmonic properties of silver to significantly enhance fluorescent imaging. Plasmonics rely on the ability of nanostructured metals such as silver to enhance the proximal electromagnetic field. As a result, fluorescent dyes appear ten times brighter in the presence of the silver nanoparticles than they do when the particles are absent.
To reduce the noise from particles that were not internalized by cells, the team developed a protocol for etching the silver nanoparticles with a mild, non-permeable solution composed of retasked chemicals commonly used to de-stain silver-stained polyacrylamide gels. The solution oxidizes and then clears away the silver, effectively dissolving the particles. What’s more, the solution is biocompatible and does not penetrate the cell membrane, allowing internalized particles to remain intact.
Particles are effective in vivo
To demonstrate the efficacy of the process, researchers targeted the nanoparticles to tumor cells in mice. C-end rule (CendR) peptides on the particles’ surface directed them to neuropilin-1 (NRP-1) receptors on cancer cells. Subsequent imaging and blood chemistry analyses verified internalization and fluorescent imaging enhancement with minimal toxicity.
Of particular relevance is the ability to remove off-target particles, allowing them to be cleared from the body. Coupled with the ability to modulate the particles’ destination by altering the surface agents, the work has implications beyond imaging, including targeted delivery of non-permeable drugs. The combined traits make them a promising and dynamic tool for future studies.
The findings were published recently in Nature Materials and can be accessed online.