Near-infrared two-zone AIE molecules facilitate lymph node imaging and surgical navigation

On July 5, 2022, Professor Wang Dong of the AIE Research Center of Shenzhen University and Professor Zhu Shoujun of Jilin University published the research results entitled “Molecular engineering of AIE luminogens for NIR-II/IIb bioimaging and surgical navigation of lymph nodes” in the Journal of Matter.

This achievement constructs a near-infrared two-region AIE molecule with the longest absorption wavelength through molecular engineering strategies, which can achieve long retention, deep penetration, and high signal-to-noise ratio sentinel lymphatic imaging and surgical navigation compared with the FDA-approved and clinically applied contrast agent indocyanine green (ICG).

Dr. Song Shanshan of Shenzhen University and Dr. Wang Yajun of Jilin University are the first authors of the paper, Academician Tang Benzhong (currently dean of the Polytechnic School of Chinese University of Hong Kong, Shenzhen), Professor Wang Dong of the AIE Research Center of Shenzhen University, and Professor Zhu Shoujun of Jilin University are the co-corresponding authors of the paper.

Sentinel lymph node imaging is critical for both cancer staging and cancer treatment decision-making. The sentinel lymph node imaging methods currently used have problems such as short retention times, poor penetration depths, and low signal-to-noise ratios. As a cutting-edge technology, near-infrared binary (NIR-II) aggregation induced emission (AIE) materials are expected to solve these problems, however, how to balance the relationship between large conjugate structures (required for long-wavelength molecules) and twisted propeller structures (to meet the properties of the AIE) to construct AIE molecules with ultra-long absorption wavelengths remains a major challenge.

Figure 1: Schematic diagram of molecular design principles, the preparation process of nanoparticles, and the application of nanoparticles in biomedicine.

In this work, Academician Tang Benzhong’s team constructed the NIR-II AIE molecule (NIR-920) with the longest absorption wavelength through molecular engineering strategies. NiR-920 nanoparticles have bright fluorescence for versatile fluorescence imaging and high-performance lymph node imaging in the NIR-II/NIR-IIb region. Compared to the FDA-approved and clinically applied contrast agent indocyanine green (ICG), NIR-920 nanoparticles have advantages such as longer retention time, deeper penetration depth, higher signal-to-noise ratio, and stronger light stability (Figure 1). Based on this, NIR-920 NPs enable quick and accurate surgical navigation of sentinel lymph nodes. This study provides an important theoretical basis for the design of AIE molecules in the NIR-II/NIR-IIb region and opens up new avenues for accelerating the clinical translation of AIE molecules in high-performance diagnostics and surgical navigation.

Figure 2: Structural and optical properties of NIR-820 and NIR-920.

The near-infrared binary AIE molecule (NIR-920) constructed by this research result achieves absorption and emission of large-span redshifts. By simply replacing the S atom in the BBTD with a Se atom, the goal of absorbing a wavelength of 100 nm with a redshift of 100 nm and an absorption of more than 900 nm in the AIE field was achieved (from NIR-820 to NIR-920). Most importantly, the tail of the molecule’s fluorescent emission peak can extend beyond 1600 nm. Such long absorption and emission provide a favorable guarantee for imaging of the NIR-II/NIR-IIb region (Figure 2).

Figure 3: Photophysical properties of NIR-920.

The NIR-920 constructed has typical AIE properties, and its two-region fluorescence brightness in the aggregate state is stronger than that of commercially available carbon nanotubes. By nano-precipitation, the AIE molecules can be encapsulated to obtain NIR-920 NPs with good water dispersion. Using IR26 as a reference, the nanoparticle has a quantum efficiency of 0.02% (Figure 3). These excellent performances give NIR-920 NPs a broad application prospect in the field of near-infrared two-region in vivo imaging.

Figure 4: Lymph node imaging and stability comparison of NIR-920 NPs and ICGs.

Compared with FDA-approved and clinically applied contrast agent ICG, NIR-920 NPs have more prominent advantages in lymph node imaging. It retains longer, penetrates deeper, has a higher signal-to-noise ratio, is more photostable, and has a unique lymph node targeting capability (Figure 4). All of these excellent properties provide sufficient protection for lymph node surgical navigation.

Figure 5: NIR-920 NPs imaging-guided sentinel lymph node surgery.

Finally, in vivo experiments demonstrated that under the NIR-II fluorescent imaging navigation of NIR-920 NPs, the sentinel lymph nodes can be accurately removed, and the biopsy results of the excised sentinel lymph nodes prove that the tumor has not metastasized. Section colocation experiments with Cy3 NPs also confirmed the clear structure of the lymph nodes (Figure 5). All the data suggest that NIR-920 NPs can be used for accurate imaging navigation sentinel lymph node resection and are able to quickly determine cancer metastasis and cancer stage. This study provides new ideas, new directions and new models for the research and development of precision lymph node surgical navigation system. (Source: Science Network)

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