Near-infrared-II ratiometric fluorescence probes for non-invasive detection and precise navigation surgery of metastatic sentinel lymph nodes

Abstract

Sentinel lymph node (SLN) biopsy is the key diagnostic procedure to determine tumor metastasis and treatment plan. Current SLN biopsy has considerable drawbacks in that SLNs (both malignant and normal) must be removed by navigation surgery, followed by a time-consuming pathological examination. The selective, non-invasive, and real-time diagnosis of metastatic status in SLNs is becoming essential. Methods: Here, we design two lanthanide-doped nanoparticles as a pair of NIR-II ratiometric fluorescence probes, one of which is conjugated with tumor-targeting moiety, while the other is conjugated with PEG as an internal reference. The NIR-II ratiometric fluorescence signal (I 1060 nm /I 1525 nm ) from two well-separated channels were used to identify the tumor-draining SLNs. The precise navigation surgery of metastatic SLNs was performed and we further evaluated their surgery outcomes. Results: The NIR-II ratiometric fluorescence facilitates an ideal fluorescence-guided surgery with only resection of tumor-positive SLNs, thereby avoiding unnecessary removal of the normal SLNs. In addition, our system has a time-saving operation procedure and can be performed under the operation light without altering the appearance of surgical settings. Conclusion: The present study enables non-invasive and real-time detection metastatic status in SLNs with high sensitivity and selectivity. Our investigations will provide a new direction for SLN biopsy and substantially improve cancer surgery outcomes.

Dye-Triplet-Sensitized Downshifting Nanoprobes with Ratiometric Dual-NIR-IIb Emission for Accurate In Vivo Detection

“…When transferred to the aqueous phase, the NIR-IIb fluorescence intensity at 1525 nm from Er 3+ ion-doped nanoprobes showed a ∼10-fold decrease upon both 980 and 808 nm excitation (Figure f). Nevertheless, the NIR-II brightness of aqueous nanoprobes was still sufficient for in vivo biological imaging despite suffering sharp fluorescence attenuation. , Because IR-808@DSNPs@DSPE-PEG-NH 2 can emit dual emissions at the same NIR-IIb wavelength, it was suitable for constructing ratiometric nanoprobes for NIR-II imaging. The ratiometric fluorescence signal (F 808ex /F 980ex ) was measured to be ∼1 and remained stable in PBS for 7 days without any variation, benefiting the long-term storage of nanoprobes (Figure g).…”

Protein@Cyanine‐Based NIR‐II Lymphography Enables the Supersensitive Visualization of Lymphedema and Tumor Lymphatic Metastasis

“…[15,16] The identification of early-stage tumor metastasis and tumor-positive LNs is becoming essential in the field of fluorescence-guided cancer surgery, preferentially through a noninvasive route. [17,18] Thus, spatiotemporal assessment of the functional status of the lymphatic system will be critical for understanding lymphatic biology, evaluating lymphatic functions, as well as diagnosing patients with lymphatic diseases.…”

Blood Circulation Assessment by Steadily Fluorescent Near-Infrared-II Aggregation-Induced Emission Nano Contrast Agents

“…Fluorescence imaging technology has been widely applied in the diagnosis and visualization of a diseased region due to its in situ, on-time, and noninvasiveness properties and so on. − Notwithstanding these advantages, its applicability in challenging in vivo physiological settings is constrained by its limited tissue penetration depth and unsatisfactory anatomical detail resolution . To overcome these challenges, fluorescence imaging in the second near-infrared wavelength range (NIR-II, 1000–1700 nm) has been developed because of the higher spatial imaging resolution (diminished autofluorescence) and deeper penetration depth (reduced photon scattering) in tissues. , NIR-II fluorescence imaging depends on highly efficient NIR-II-emissive fluorophores. , Compared to inorganic fluorophores, the organic NIR-II luminogens hold the advantages of tunable photophysical characteristics, a clear structure–property relationship, and satisfactory biocompatibility − and thus are promising for various in vivo imaging applications like angiography, lymphangiography, sentinel-lymph-node localization, and imaging-guided surgery . It is thus anticipated that NIR-II imaging may serve as an ideal tool to gain accurate anatomical and hemodynamic information.…”

“…15,16 NIR-II fluorescence imaging depends on highly efficient NIR-II-emissive fluorophores. 17,18 Compared to inorganic fluorophores, the organic NIR-II luminogens hold the advantages of tunable photophysical characteristics, a clear structure−property relationship, and satisfactory biocompatibility 19−21 and thus are promising for various in vivo imaging applications like angiography, 22 lymphangiography, 23 sentinellymph-node localization, 24 and imaging-guided surgery. 11 It is thus anticipated that NIR-II imaging may serve as an ideal tool to gain accurate anatomical and hemodynamic information.…”