Abstract
Strategies for selectively imaging and delivering drugs to tumours typically leverage differentially upregulated surface molecules on cancer cells. Here, we show that intravenously injected carbon quantum dots, functionalized with multiple paired α-carboxyl and amino groups that bind to the large neutral amino acid transporter 1 (which is expressed in most tumours), selectively accumulate in human tumour xenografts in mice and in an orthotopic mouse model of human glioma. The functionalized quantum dots, which structurally mimic large amino acids and can be loaded with aromatic drugs through π–π stacking interactions, enabled—in the absence of detectable toxicity—near-infrared fluorescence and photoacoustic imaging of the tumours and a reduction in tumour burden after the targeted delivery of chemotherapeutics to the tumours. The versatility of functionalization and high tumour selectivity of the quantum dots make them broadly suitable for tumour-specific imaging and drug delivery.
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Data availability
The main data supporting the results in this study are available within the Article and its Supplementary Information. The raw and analysed datasets that were generated during the study are too large to be publicly shared, but they are available for research purposes from the corresponding authors on reasonable request.
Change history
04 May 2020
Editor’s note: The editors of Nature Biomedical Engineering have been notified about issues with a few images in this Article. Two micrographs within Fig. 4 and Supplementary Figs. 20, 25 and 61 are duplicated. In addition, a few of the mice panels in Figs. 2c and Supplementary Figs. 29, 31, 37 and 56 appear to be duplicates. The authors have informed us that these are inadvertent errors and believe that the overall data and conclusions are solid, and that they need to retrieve data from the Cell Imaging Facility and Animal Imaging Facility at Beijing Normal University before they can fully clarify the image issues. They have also informed us that access to the data will be delayed because of COVID-19 access restrictions.
21 January 2022
A Correction to this paper has been published: https://doi.org/10.1038/s41551-022-00845-x
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Acknowledgements
This work was supported by NSFC grants (numbers 21573019 and 21872010, to L.F.), a NSFC Major Research Plan grant (number 21233003, to L.F.), a NSFC grant (21773016, to J.Zhu) and NIH grants (NS095817 and NS110721, to J.Zhou).
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L.F., J.Zhu, S.L., W.S., H.W. and J.Zhou designed the experiments. S.L., W.S., H.W., T.Y., C.Y., J.L., G.D., F.Y., S.Z., Y.L., X.L., H.T., A.T.C., F.L. and Y.Z. performed the experiments. All of the authors were involved in the analyses and interpretation of data. S.L., L.F. and J.Zhou wrote the paper, with help from the co-authors.
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Supplementary Video 1
Penetration of LAAM TC-CQDs into HeLa cells.
Supplementary Video 2
Penetration of LAAM TC-CQDs into CCC-ESF-1 cells.
Supplementary Video 3
Three-dimensional reconstruction of FL images of LAAM TC-CQDs in mice bearing HeLa tumours.
Supplementary Video 4
Three-dimensional reconstruction of FL images of G-CQDs in mice bearing HeLa tumours.
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Li, S., Su, W., Wu, H. et al. Targeted tumour theranostics in mice via carbon quantum dots structurally mimicking large amino acids. Nat Biomed Eng 4, 704–716 (2020). https://doi.org/10.1038/s41551-020-0540-y
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DOI: https://doi.org/10.1038/s41551-020-0540-y
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