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How can we ensure that life-saving drugs or genetic therapies reach their intended target cells without causing harmful side effects? Researchers at Helmholtz Munich, Ludwig-Maximilians-Universität (LMU), and Technical University Munich (TUM) have taken an important step to answer this question.
How can we ensure that life-saving drugs or genetic therapies reach their intended target cells without causing harmful side effects? Researchers at Helmholtz Munich, Ludwig-Maximilians-Universität (LMU) and Technical University Munich (TUM) have taken an important step to answer this question. They have developed a method that, for the first time, enables the precise detection of nanocarriers – tiny transport vehicles – throughout the entire mouse body at a single-cell level. This innovation, called “Single-Cell Profiling of Nanocarriers” or short “SCP-Nano”, combines advanced imaging with artificial intelligence to provide unparalleled insights into the functionality of nanotechnology-based therapies. The results, published in Nature Biotechnology, pave the way for safer and more effective treatments, including mRNA vaccines and gene therapies.
The Role of Nanocarriers in Modern Medicine
Nanocarriers will play a central role in the next wave of life-saving medicines. They enable the targeted delivery of drugs, genes, or proteins to cells within patients. With SCP-Nano, researchers can analyze the distribution of extremely low doses of nanocarriers throughout the entire mouse body, visualizing each cell that has taken them up. SCP-Nano combines optical tissue clearing, light-sheet microscopy imaging, and deep-learning algorithms. First, whole mouse bodies are made transparent. After the three-dimensional imaging of whole mouse bodies, nanocarriers within the transparent tissues can then be identified down to the single-cell level. By integrating AI-based analysis, researchers can quantify which cells and tissues are interacting with the nanocarriers and precisely where this occurs.
Practical Applications of SCP-Nano
Examples of nanocarriers analyzed by Ali Ertürk, the director of the Institute for Intelligent Biotechnologies (iBIO) at Helmholtz Munich, and his team using SCP-Nano include lipid nanoparticles (LNPs), DNA origami structures and adeno-associated viruses (AAVs). These nanocarriers are essential for modern therapeutics that address diseases at their cellular roots, each possessing unique properties that make them suitable for different applications. DNA origami structures are easily programmable and AAVs are highly efficient carriers for gene therapy. The LNPs facilitate RNA delivery, which underlies modern mRNA vaccines and a broad range of other RNA therapeutics. Using SCP-Nano, the researchers demonstrated that DNA origami structures can be preferentially targeted to the immune cells, while AAV variants target distinct brain regions and adipose tissue. Importantly, the platform also revealed that lipid nanoparticles carrying mRNA therapeutics can accumulate in heart tissue. Thus, using SCP-Nano researchers can now detect potentially problematic off-target tissues and associated toxicities before they enter clinical trials, paving the way for the development of safer mRNA therapeutics.
Visualizing Nanocarriers with Unprecedented Precision
“With SCP-Nano, we can detect nanocarriers throughout the body in incredibly low doses, down to 0.0005 mg/kg,” says the study's first author, Dr. Jie Luo. “This gives us an entirely new perspective on how these tiny transport vehicles interact with organs and cells.” Luo emphasizes that it is especially important that SCP-Nano can identify unwanted accumulation in the heart or liver.
The mechanism of nanocarriers is comparable to a parcel delivery service, Ertürk explains: “Each nanocarrier is like a package carrying an important payload that must be delivered to the exact right apartment, not just the one next door. SCP-Nano allows us to track exactly where these packages are delivered, whether they reach their precise intended destination, or if they accidentally end up in unwanted locations.”
Driving Innovation in Personalized Medicine
SCP-Nano allows researchers to precisely identify where nanocarriers accumulate and to visualize their interactions with target cells– a key requirement for safe and effective nanocarrier applications. “SCP-Nano will not only help assess the safety of existing nanocarriers but also drive the development of new, highly targeted applications,” says Luo. “The platform can also help to monitor the success of mRNA therapies or detect potential side effects early.”
A New Era for Drug Development and Personalized Therapies
By combining cutting-edge imaging and AI technologies, SCP-Nano offers researchers and clinicians a new level of understanding of how therapies interact with the body and can easily be extended to human tissues and organs. “Precision medicine and targeted delivery are often discussed, but scalable and effective tools for this have been limited. This new approach offers a solution to a key challenge in drug development,” concludes Prof. Ertürk.
With its potential to minimize side effects and enhance treatment precision, SCP-Nano marks an important step toward safer and more effective therapies in fields like cancer treatment, gene therapy, and vaccine development. This innovation not only addresses major challenges in the development of nanocarrier-based technologies but also drives the future of precision medicine.
About the Researchers
Prof. Ali Ertürk is Director of the Institute for Intelligent Biotechnologies at Helmholtz Munich and a professor at Ludwig-Maximilians-Universität München (LMU). He is part of the Munich Cluster for Systems Neurology (SyNergy).
Dr. Jie Luo is a researcher at the Institute for Intelligent Biotechnologies at Helmholtz Munich and at LMU.
About Helmholtz Munich
Helmholtz Munich is a leading biomedical research center. Its mission is to develop breakthrough solutions for better health in a rapidly changing world. Interdisciplinary research teams focus on environmentally triggered diseases, especially the therapy and prevention of diabetes, obesity, allergies, and chronic lung diseases. With the power of artificial intelligence and bioengineering, researchers accelerate the translation to patients. Helmholtz Munich has around 2,500 employees and is headquartered in Munich/Neuherberg. It is a member of the Helmholtz Association, with more than 43,000 employees and 18 research centers the largest scientific organization in Germany. More about Helmholtz Munich (Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt GmbH): www.helmholtz-munich.de/en
Prof. Ali Ertürk
Email: ali.erturk@helmholtz-munich.de
Luo, Molbay, Chen, Horvath, Kadletz, Kick, Zhao et al., 2025: Deep Learning Powered Imaging of Nanocarriers Across Entire Mouse Bodies at Single-Cell Resolution. Nature Biotechnology. DOI: 10.1038/s41587-024-02528-1
https://www.nature.com/articles/s41587-024-02528-1
Lipid nanoparticles visualized using SCP-Nano technology at the cellular level in lung tissue.
Ali Ertürk
Helmholtz Munich / Ali Ertürk
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Lipid nanoparticles visualized using SCP-Nano technology at the cellular level in lung tissue.
Ali Ertürk
Helmholtz Munich / Ali Ertürk
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