Pang, Z orcid.org/0000-0003-3949-4928, Yan, W, Yang, J et al. (4 more authors) (2022) Multifunctional gold nanoclusters for effective targeting, near-infrared fluorescence imaging, diagnosis, and treatment of cancer lymphatic metastasis. ACS Nano, 16 (10). pp. 16019-16037. ISSN 1936-0851
Abstract
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 99mTc-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 dual-ligand-/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 Au25(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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2022 The Authors. Published by American Chemical Society. This is an open access article, under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) |
Keywords: | gold nanoclusters; cancer metastasis; lymph-node targeting; fluorescence imaging; imaging-guided surgery; theranostics |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Engineering & Physical Sciences (Leeds) > School of Chemistry (Leeds) > Inorganic Chemistry (Leeds) The University of Leeds > Faculty of Environment (Leeds) > School of Food Science and Nutrition (Leeds) > FSN Chemistry and Biochemistry (Leeds) |
Funding Information: | Funder Grant number BBSRC (Biotechnology & Biological Sciences Research Council) BB/R007829/1 Royal Society IEC\NSFC\191397 |
Depositing User: | Symplectic Publications |
Date Deposited: | 10 Aug 2022 15:56 |
Last Modified: | 31 Jan 2023 14:31 |
Status: | Published |
Publisher: | American Chemical Society |
Identification Number: | 10.1021/acsnano.2c03752 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:189867 |