期刊
ACS NANO
卷 16, 期 10, 页码 16019-16037出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.2c03752
关键词
gold nanoclusters; cancer metastasis; lymph-node targeting; fluorescence imaging; imaging-guided surgery; theranostics
类别
资金
- Ministry of Science and Technology of China [2020YFA0908900]
- Shenzhen Science and Technology Program [KQTD20190929172743294]
- National Natural Science Foundation of China [22104050, 21535001, 21761142006]
- Chinese Academy of Sciences [QYZDJ-SSW-SLH039]
- Guangdong Innovative and Entrepreneurial Research Team Program [2019ZT08Y191]
- UK Biotechnology and Biological Sciences Research Council [BB/R007829/1]
- Royal Society [IEC\NSFC\191397]
Developing effective lymph-node targeting and imaging probes is crucial for the early detection and diagnosis of tumor metastasis. Researchers have developed dualligand-/multiligand-capped gold nanoclusters (GNCs) that can specifically target LN cancer metastasis and provide near-infrared fluorescence imaging, diagnosis, and treatment.
Developing effective lymph-node (LN) targeting and imaging probes is crucial for the early detection and diagnosis of tumor metastasis to improve patient survival. Most current clinical LN imaging probes are based on small organic dyes (e.g., indocyanine green) or radioactive Tc-99m-complexes, which often suffer from limitations, such as rapid photobleaching, poor signal contrast, and potential biosafety issues. Moreover, these probes cannot easily incorporate therapeutic functions to realize beneficial theranostics without affecting their LN-targeting ability. Herein, we have developed dualligand-/multiligand-capped gold nanoclusters (GNCs) for specific targeting, near-infrared (NIR) fluorescence imaging, diagnosis, and treatment of LN cancer metastasis in in vivo mouse models. By optimizing the surface ligand coating, we have prepared Au-25(SR1)(n)(SR2)(18-n) (where SR1 and SR2 are different functional thiol ligands)-type GNCs, which display highly effective LN targeting, excellent stability and biocompatibility, and optimal body-retention time. Moreover, they can provide continuous NIR fluorescence imaging of LNs for >3 h from a single dose, making them well-suited for fluorescence-guided surgery. Importantly, we have further incorporated methotrexate, a chemotherapeutic drug, into the GNCs without affecting their LN-targeting ability. Consequently, they can significantly improve the efficiency of methotrexate delivery to target LNs, achieving excellent therapeutic efficacy with up to 4-fold lower hepatotoxicity. Thus, the GNCs are highly effective and safe theranostic nanomedicines against cancer lymphatic metastasis.
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