Amour plating nanoprobes

The Adolphe Merkle Institute's BioNanomaterials group has developed an innovative method to help tiny tracers, used to study how nanoparticles behave in biological environments, resist chemical degradation, promising more reliable data for diagnostic nanomedicine.

To understand how nanoparticles behave in cells and tissues, researchers have relied on a tool known as a multimodal tracer. This probe emits a signal across two or more imaging techniques. Some of these nanoparticles, for example, are designed to fluoresce under laser light and reveal their structure when examined with an electron beam microscope. One of the most promising of these tracers is silica-coated gold nanoparticles, owing to their good biocompatibility, ease of synthesis, and versatility across different imaging techniques. But this approach has an unexpected weak point. One might assume the danger lies inside the cell, in the acidic compartments the particle eventually reaches. In fact, the shells hold up well there. The real damage happens earlier, outside the cell, in the protein- and ion-rich fluid the particle must cross on its way in. In that fluid, water slowly breaks apart the silica shell, and the surrounding pH, ions, and serum proteins all accelerate the process, causing the shell to fragment, leak its dye, and give unreliable signals. The researchers found that particles prepared for cellular imaging lost their shells entirely within 16 hours in this medium.

The AMI researchers turned to nature for a solution. Diatoms, tiny water-borne algae with intricate glass-like shells, don't build their durable structures in a single step. They first lay down a soft, gel-like silica framework that matures over time. The reactive groups on its surface condense into a dense, tightly bonded siloxane network, far more resistant to chemical attack than the fragile material it started as. The team set out to do the same with their nanoparticles. "Translating this principle to synthetic materials enabled us to create imaging probes that remain stable and reliable in complex biological environments," explains the AMI BioNanomaterials Co-Chair, Prof. Alke Petri-Fink.

The scientists adopted this framework-first approach, not unlike brickmaking. Make a brick from its constituent elements and then fire it in a kiln to give it strength and longevity. In the case of nanoparticles, the silica shell was hardened through calcination, in which the coated particles were heated to 800 degrees Celsius. This eliminated almost all of the reactive silanol groups that make the shell vulnerable to dissolution. Only then were the nanoparticles functionalized with fluorescent dyes, transforming them into finished nanoprobes.

Processing the particles this way brought a real advantage for imaging. With conventional probes, a bright signal can be misleading, since once the shell falls apart, the loose dye continues to glow even after the particle itself is gone. Because the stabilized shells stay whole, their fluorescence reliably marks a real, intact particle. This allowed the researchers to combine two views of the same particle, using its glow to quickly locate where particles are and its dense gold core to pinpoint them precisely under an electron microscope. In crowded regions, where fluorescence alone blurs particles together and can no longer distinguish them, the gold cores remained individually visible, maintaining accurate counts where light-based imaging fails.

Bio-inspired, matured structures for durable nanoprobes could be a new standard for nanomedicine research, says Fink. "These tracers finally allow us to follow nanoparticles inside cells with the certainty that what we see is real, an intact particle, not a signal left behind by one that has already fallen apart."

Reference:

Lee, W. S.; Lee, H.; Taladriz-Blanco, P.; Vanhecke, D.; Rothen-Rutishauser, B.; Petri-Fink, A. Bioinspired Stabilization of Fluorescent Au@SiO2 Tracers for Multimodal Biological Imaging. Advanced Functional Materials 2025, e27555.