Fluorescence imaging in the second near-infrared window (NIR-II) offers a powerful way to visualize biological structures deep inside living tissue. Compared with visible light, NIR-II light undergoes less tissue scattering and generates lower autofluorescence, making it particularly suitable for resolving blood vessels and other fine structures.
Many organic NIR-II fluorophores, however, are highly hydrophobic and require nanoscale carriers for dispersion in aqueous biological environments. Conventional amphiphilic polymer carriers can effectively solubilize these dyes, but structural destabilization under dilution or in biological fluids may lead to dye leakage, increasing background fluorescence and reducing imaging contrast.
A research team led by Aijun Tong and Yu Xiang at Tsinghua University has developed a DNA-based nanocarrier to address this stability challenge. The researchers engineered DNA amphiphiles bearing multiple tetraphenylethylene (TPE) units. Cooperative hydrophobic interactions and aromatic π–π stacking among neighboring TPE groups drove the formation of highly stable DNA nanoaggregates.
The study has been published online as a Just Accepted article in Nano Research on August 5, 2026 and is available through SciOpen.
“Bright fluorescence alone is not sufficient for high-quality in vivo imaging. The carrier also needs to retain the fluorophore within a stable nanoscale environment,” said corresponding author of the study. “By introducing multiple TPE units, we were able to use cooperative molecular interactions to reinforce the DNA assembly.”
The researchers prepared DNA amphiphiles containing three, five, seven, or nine TPE units and found that the seven-TPE construct provided the best balance between structural stability and synthetic practicality. The resulting 7-TPE-DNA formed spherical nanoaggregates with a hydrodynamic diameter of approximately 17.5 nanometers. Unlike conventional C18-DNA and cholesterol-DNA assemblies, the 7-TPE-DNA nanoaggregates remained assembled under denaturing conditions containing urea or SDS.
The TPE-rich hydrophobic core also served as a compartment for loading NIR-II fluorophores. Among five representative hydrophobic dyes tested, the aggregation-induced-emission-active fluorophore TPE-BBT produced the strongest fluorescence. The resulting 7-TPE-DNA@TPE-BBT nanoprobe exhibited an absolute photoluminescence quantum yield of 2.45% in aqueous solution.
The researchers then compared the DNA carrier with PEG- and F127-based formulations. Under matched TPE-BBT loading conditions, 7-TPE-DNA achieved a dye-loading level comparable to PEG while showing substantially greater resistance to dye leakage. After extraction with ethyl acetate and n-butanol, the DNA nanoprobe retained approximately 80% and 60% of its initial fluorescence, respectively, whereas the PEG formulation retained only about 18% and 2%. The F127 formulation lost nearly all detectable fluorescence.
This enhanced dye retention translated into improved vascular imaging in living mice. Following intravenous administration, 7-TPE-DNA@TPE-BBT clearly visualized the femoral artery with low background fluorescence. Quantitative analysis showed a signal-to-background ratio higher than that of the PEG-based and F127-based control. The nanoprobe also resolved dense subcutaneous capillary networks that were difficult to distinguish with the control formulations.
An additional advantage of the platform is that the hydrophilic DNA segment remains accessible for sequence-specific hybridization, creating opportunities to introduce complementary strands carrying targeting ligands, therapeutic molecules, or additional imaging components.
The researchers suggest that multivalent molecular engineering could provide a general strategy for stabilizing DNA amphiphiles and related supramolecular imaging systems, with potential applications in targeted imaging, multimodal diagnostics, and multifunctional nanomedicine. The work was supported by the National Key R&D Program of China (grant no. 2021YFA1200900) .
Other contributors to the study include Min Zhou, Ying Wang, Chu Zhang, Zichen Qin and Zicong Liang from the Department of Chemistry at Tsinghua University, and Zhiguo Fang and Yeteng Zhong from the National Center for Nanoscience and Technology.
DOI Link:
https://doi.org/10.26599/NR.2026.94909091
About Nano Research
Nano Research is a peer-reviewed, open access, international and interdisciplinary research journal, sponsored by Tsinghua University and the Chinese Chemical Society, published by Tsinghua University Press on the platform SciOpen. It publishes original high-quality research and significant review articles on all aspects of nanoscience and nanotechnology, ranging from basic aspects of the science of nanoscale materials to practical applications of such materials. After 18 years of development, it has become one of the most influential academic journals in the nano field. Nano Research has published more than 1,000 papers every year from 2022, with its cumulative count surpassing 8,000 articles. In 2025 InCites Journal Citation Reports, its 2025 IF is 9.4 (8.3, 5 years), and it continues to be the Q1 area among the four subject classifications. Nano Research Award, established by Nano Research together with TUP and Springer Nature in 2013, and Nano Research Young Innovators (NR45) Awards, established by Nano Research in 2018, have become international academic awards with global influence.
Nano Research
Multivalent TPE engineering stabilizes DNA nanoprobes for bright NIR-II vascular imaging
5-Aug-2026