Journal
CHEMISTRY-A EUROPEAN JOURNAL
Volume 27, Issue 14, Pages 4670-4675Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/chem.202005000
Keywords
cell-penetrating peptide; cytosolic delivery; gold nanorod; near-infrared irradiation
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Funding
- MINECO-FEDER [BIO2016-75327-R]
- Generalitat de Catalunya (XRB) [2017SGR0998]
- Fondap [15130011]
- IN2UB [ART2019-25173]
- la Caixa Foundation [LCF/PR/GN14/10270002]
- MINECO (Government of Spain)
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By utilizing the unique photothermal properties of gold nanorods, combined with modifications of cell-penetrating peptide and nuclear targeting on proteins and AuNRs, and achieving spatiotemporal control of protein release within the safe biological window through near-infrared laser irradiation, cytosolic protein delivery has been successfully triggered.
Cytosolic protein delivery remains elusive. The inability of most proteins to cross the cellular membrane is a huge hurdle. Here we explore the unique photothermal properties of gold nanorods (AuNRs) to trigger cytosolic delivery of proteins. Both partners, protein and AuNRs, are modified with a protease-resistant cell-penetrating peptide with nuclear targeting properties to induce internalization. Once internalized, spatiotemporal control of protein release is achieved by near-infrared laser irradiation in the safe second biological window. Importantly, catalytic amounts of AuNRs are sufficient to trigger cytosolic protein delivery. To the best of our knowledge, this is the first time that AuNRs with their maximum of absorption in the second biological window are used to deliver proteins into the intracellular space. This strategy represents a powerful tool for the cytosolic delivery of virtually any class of protein.
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