Phosphorylcholine-conjugated gold-molecular clusters improve signal for Lymph Node NIR-II fluorescence imaging in preclinical cancer models

Abstract

Sentinel lymph node imaging and biopsy is important to clinical assessment of cancer metastasis, and novel non-radioactive lymphographic tracers have been actively pursued over the years. Here, we develop gold molecular clusters (Au25) functionalized by phosphorylcholine (PC) ligands for NIR-II (1000–3000 nm) fluorescence imaging of draining lymph nodes in 4T1 murine breast cancer and CT26 colon cancer tumor mouse models. The Au-phosphorylcholine (Au-PC) probes exhibit ‘super-stealth’ behavior with little interactions with serum proteins, cells and tissues in vivo, which differs from the indocyanine green (ICG) dye. Subcutaneous injection of Au-PC allows lymph node mapping by NIR-II fluorescence imaging at an optimal time of ~ 0.5 − 1 hour postinjection followed by rapid renal clearance. Preclinical NIR-II fluorescence LN imaging with Au-PC affords high signal to background ratios and high safety and biocompatibility, promising for future clinical translation.

Slice Visualization for Imaging Nanocluster Transformations

“…Considering that (i) the Au 1 Ag 24 (SR) 18 nanocluster was composed of an icosahedral Au 1 Ag 12 kernel that was wrapped by six identical Ag 2 (SR) 3 dimeric motif structures and (ii) both Au 1 Ag 24 (SR) 18 and Au 1 Ag 30 (SR) 20 clusters contained the same Au 1 Ag 12 kernel, we proposed that the introduced Ag-SR complexes induced the assembly of the peripheral motif structures of Au 1 Ag 24 (SR) 18 while retaining its Au 1 Ag 12 kernel. Accordingly, some cluster intermediates should exist during the transformation from Au 1 Ag 24 (SR) 18 to Au 1 Ag 30 (SR) 20 . However, given the rapid conversion from Au 1 Ag 24 (SR) 18 to Au 1 Ag 30 (SR) 20 (within 1 min) and the heterogeneous reaction between Au 1 Ag 24 (SR) 18 and Ag-SR complexes (insolubility of Ag-SR complexes), the intermediates were extremely difficult to monitor.…”

“…Accordingly, some cluster intermediates should exist during the transformation from Au 1 Ag 24 (SR) 18 to Au 1 Ag 30 (SR) 20 . However, given the rapid conversion from Au 1 Ag 24 (SR) 18 to Au 1 Ag 30 (SR) 20 (within 1 min) and the heterogeneous reaction between Au 1 Ag 24 (SR) 18 and Ag-SR complexes (insolubility of Ag-SR complexes), the intermediates were extremely difficult to monitor. In addition, the reaction between Au 1 Ag 24 (SR) 18 and Ag-SR was challenging to terminate since the solid-state complex continually interacted with the Au 1 Ag 24 (SR) 18 cluster even after termination of the reaction.…”

Recent progress of second near-infrared (NIR-II) fluorescence microscopy in bioimaging

“…With the improvement of detector performance and the development of new fluorescent probes, in vivo NIR-II fluorescence imaging has become a research hotspot ( Li et al, 2022a ; Baghdasaryan et al, 2022 ; Niu et al, 2022 ; Xu et al, 2022 ; Liu et al, 2023 ). The first in-vivo NIR-II fluorescence imaging was achieved by Hongjie Dai in 2009 ( Welsher et al, 2009 ).…”

The location of metastatic lymph nodes and the evaluation of lymphadenectomy by near-infrared photoacoustic imaging with iridium complex nanoparticles

“…3 Therefore, sentinel lymph node imaging and biopsy is important for the clinical assessment of cancer metastasis. 4 Lymphadenectomy is the surgical removal of the sentinel lymph node or more lymph nodes that can support accurate staging and evaluation of metastasis. 5 Pre-operative identification of metastatic lymph nodes will avoid unnecessary lymph node dissection, significantly shorten the operation time, and reduce postoperative complications.…”

“…4 Lymphadenectomy is the surgical removal of the sentinel lymph node or more lymph nodes that can support accurate staging and evaluation of metastasis. 5 Pre-operative identification of metastatic lymph nodes will avoid unnecessary lymph node dissection, significantly shorten the operation time, and reduce postoperative complications. 6 Therefore, it is essential to find better materials and more preferred imaging methods to detect lymph nodes.…”