Hybrid Nano-probe Can Detect Live Cancer Cells

A new hybrid nano-probe that could lead to noninvasive detection and treatment of cancer at the level of a single cell has been developed by a University of Southern California scientist.

Fabien Pinaud, assistant professor of biological sciences, chemistry and physics and astronomy at USC Dornsife, created a method for amplifying a biochemical signal on the surface of cancer cells.

The new technique binds and assembles gold nanoparticles in living cells using two fragments of a fluorescent protein as “molecular glue.” These tiny probes act as amplifiers, enhancing researchers’ ability to detect distinct biomarkers — things like overexpressed or mutated proteins — found in cancer cells.

The boosted signal allows the scientists to distinguish cancer cells from healthy cells through the use of Raman spectroscopy — a specialized laser imaging technique.

Molecular Glue Assemblies

Using “molecular glue” assemblies to design novel nano-probes is common practice in biomedical research today, but most scientists build these with DNA rather than protein. While promising optical probes are being generated using DNA assemblies in test tubes, DNA is not a practical adhesive in live cells.

Proteins are often better.

“Our approach takes advantage of the fact that we have two different nanoparticles which, on their own, are not active, but which become active when they assemble on cancer cells,”

said Pinaud, principle investigator of the Single Molecule Biophotonics Group and co-author of a related study.

Pinaud and his team start with a fluorescent protein, one that glows when ultraviolet-blue light shines on it. The fluorescent protein is split into two fragments and each piece is attached to a set of gold nanoparticles.

hybrid nanoprobe

Credit: Fabien Pinaud

Both sets of nanoparticles zero-in on cells and bind specifically to biomarkers at the cell surface. As the nanoparticles collide on a cancer cell, the protein fragments naturally reassemble into the whole fluorescent protein.

Restructuring Advantages

The restructuring process provides two advantages. First, the activation of a new biochemical signal in the fluorescent protein is massively amplified by the nanoparticles, which allows for detection by Raman imaging.

Second, heat and ultrasounds are produced when the laser hits the nanoparticles, and that can be measured with ultrasound detectors. This dual effect provides high confidence that a detected cell is actually cancerous and not a false-positive signal from a healthy cell.

Photoacoustic imaging of in situ assembled split-FP AuNP clusters on cells.

Photoacoustic imaging of in situ assembled split-FP AuNP clusters on cells.
Credit: Tuğba Köker, et al. CC-BY

Scientists will next explore the possibility of destroying individual cancer cells, while leaving healthy cells unharmed, by using the laser to heat up the nanoparticles.

“Going from imaging to killing cells is just about turning the knob on the laser that you use,”

Pinaud said.

The work was supported by the National Science Foundation, Division of Material Research, the Natural Sciences and Engineering Research Council of Canada (NSERC), Canada Research Chair, and the Ministère du Québec de l’Économie, Science et Innovation.

Original Paper: Cellular imaging by targeted assembly of hot-spot SERS and photoacoustic nanoprobes using split-fluorescent protein scaffolds

Top Image: Matthew Savino