“Invisible Tattoo” Composed of Gold Nanoparticles Transforms Medical Diagnostics

“Invisible Tattoo” Composed of Gold Nanoparticles
Nanoparticles of gold embedded in a permeable hydrogel can be used as medical sensors by implanted under the skin. The sensor is similar to an invisible tattoo showing concentration differences of substances in the blood by changing color. Source: ill./©: Nanobiotechnology Group, JGU Department of Chemistry

Nanoparticles of gold change Color under the skin show concentration differences of substances in the body.

The concept of implantable sensors that continuously transmit data on concentrations of substances or drugs and essential values in the body has attracted scientists and physicians for a long time. Such sensors allow the continuous monitoring of therapeutic success and disease progression. Though, these implantable sensors have to be replaced after a few days or weeks as they have not been suitable to remain in the body permanently. On the one hand, the sensor’s color which shows concentration changes has been unpredictable so far and disappeared over time. On the other hand, there is the problem of implant denial as the body identifies the sensor as a foreign object.

Researchers at Johannes Gutenberg University Mainz (JGU) have designed a unique kind of implantable sensor that can be embedded in the body for many months. The gold nanoparticles sensor is based on color-stable that are transformed with receptors for particular molecules. Inserted into a synthetic polymeric tissue, the nanogold is embedded under the skin where it reports changes in drug concentrations by switching its color.

Implantation depth. HE-stained 10μm cross-section of rat skin with the integrated macro porous implant in the subcutaneous skin layer after two months of implantation. Cells appear pink, cell nuclei blue and the macroporous hydrogel appears white. The dashed black line marks the surface of the implant. The white arrow indicates the implantation depth of 1. 3mm. Scale bar 200μm. Source: ill./©: Nanobiotechnology Group, JGU Department of Chemistry

Implant reports data as an “invisible tattoo”

A research team of professor Carsten Sönnichsen’s at JGU has been working on gold nanoparticle sensors to identify small masses of proteins in microscopic flow cells for many years. Gold nanoparticles function similarly to small antennas for light: They completely grasp and scatter it and, therefore, seem colorful. They respond to variations in their surrounding by varying colors. Sönnichsen’s team has used this theory for embedded medical sensing.

To block the small particles from moving away or being deteriorated by immune cells, they are implanted in a permeable hydrogel with a tissue-like texture. Once embedded under the skin, small cells and blood vessels pass into the pores. The sensor is combined with the tissue and is not declined as an external body. “Our sensor is like an invisible tattoo, thinner than one millimeter and not much bigger than a penny,” said Professor Carsten Sönnichsen, head of the Nanobiotechnology Group at JGU. Since the gold nanoparticles are not visible, they are infrared. However, a unique type of measurement tool can identify their color noninvasively through the skin.

In their research published in Nano Letters, for the experiment purpose, the JGU scientist employed hairless rats and embedded their gold nanoparticle sensors under the skin of rats. Color changes in these sensors were continuously observed following the execution of several doses of an antibiotic. Bloodstream carried drug molecules to the sensor. By adhering to specific receptors on the covering of the gold nanoparticles, they cause a color change that is reliant on drug concentration. Thanks to the tissue-integrating hydrogel and color-stable gold nanoparticles, the sensor was found to remain optically and mechanically steady over many months.

The huge potential of gold nanoparticles as long-lasting implantable medical sensors

“First we have used bleaching techniques to colored objects over time. However, Gold nanoparticles, do not bleach but maintain their color permanently. As they can be quickly painted with multiple receptors, they are an absolute platform for implantable sensors,” said Dr. Katharina Kaefer, leading author of the research.

The unique idea is generalizable and has the potential to prolong the endurance of implantable sensors. In the future, gold nanoparticle-based implantable sensors could be utilized to examine concentrations of various drugs or biomarkers in the body together. Such sensors could find a spot in medical research, or drug development, personalized medicine, such as the control of chronic diseases.

Interdisciplinary teamwork brought success

Sönnichsen had the plan of employing gold nanoparticles as implanted sensors already in 2004 when he began his study in biophysical chemistry as a junior professor in Mainz. Yet, the project was not accomplished until ten years succeeding in cooperation with Dr. Katharina Kaeferand Dr. Thies Schroeder, both researchers at JGU. Kaefer was looking for an interesting project for her doctorate and was especially interested in the complicated and interdisciplinary nature of the project. Initial outcomes headed to a stipend awarded to Kaefer by the Max Planck Graduate Center (MPGC) as well as financial support from Stiftung Rheinland-Pfalz für Innovation. Schroeder was experienced in laboratory animal science and biological research and had already finished several years of study work in the USA. 

“Such a project needs several people with diverse scientific backgrounds. With time we were able to convince more and more people to join us,” said Sönnichsen happily. Eventually, it was the interdisciplinary collaboration that ended in the prosperous development of the first operative implanted sensor with gold nanoparticles.

Reference: “Implantable Sensors Based on Gold Nanoparticles for Continuous Long-Term Concentration Monitoring in the Body” by Katharina Kaefer, Felix Schlapp, Sirin Celiksoy, Axel Heimann, Hüseyin Uzun, Katja Krüger, Thies Schroeder, Oliver Kempski and Carsten Sönnichsen, and Bastian Flietel, 30 March 2021, Nano Letters.

DOI: 10.1021/acs.nanolett.1c00887

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