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Gold nanoparticles (AuNPs) assembled with fluorescent peptides through Au-S bonds (pep-AuNPs) have been widely used in biomolecular detection. However, due to the endo/lysosomal trapping after the nanoprobes enter cells, the direct delivery of AuNP probes into the cytoplasm for real-time imaging remains a difficult barrier for many cytoplasm-targeting agents. Here, we prepare AuNP@gel by wrapping a multi-functional nanogel structure on the surface of a single AuNP probe by in-situ polymerization in order to directly deliver AuNP probes into the cell cytoplasm. Compared with the pep-AuNP probes, which are trapped inside lysosomes for long periods, the AuNP@gel probes use the proton-sponge effect to effectively disrupt endo/lysosomal membranes and remain in the cytoplasm. In addition, the AuNP@gel probes rapidly escape from endo/lysosomes to avoid the complex environment that interferes with the stability of the AuNP probes and the lysosomal-storage trigger the upregulation of oxidative stress into the cells. The nanogel structure enables the AuNP probes to avoid some detrimental effects and to achieve high-fidelity fluorescence signals in the cells. Compared to traditional strategies for lysosomal escape, this one-step in-situ polymerization procedure avoids the complicated modification of additional ligands and is generally applicable to peptide-, DNA-, and polymer-linked AuNP probes.

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Publication history

Received: 20 December 2019
Revised: 07 February 2020
Accepted: 09 February 2020
Published: 06 March 2020
Issue date: March 2020

Copyright

© Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature 2020

Acknowledgements

We acknowledge the support from the National Natural Science Foundation of China (No. 21775075), the Fundamental Research Funds for Central Universities (China), and the Thousand Youth Talents Plan of China. Finally, we dedicate this work to the 100th anniversary of Nankai University.

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Reprints and Permission requests may be sought directly from editorial office.
Email: nanores@tup.tsinghua.edu.cn

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