Reversible control of protein corona formation on gold nanoparticles using host-guest interactions

Jesús Mosquera, Isabel García, Malou Henriksen-Lacey, Miguel Martínez-Calvo, Mónica Dhanjani, José L. Mascarenãs, Luis M. Liz-Marzán

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)
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When nanoparticles (NPs) are exposed to biological media, proteins are adsorbed, forming a so-called protein corona (PC). This cloud of protein aggregates hampers the targeting and transport capabilities of the NPs, thereby compromising their biomedical applications. Therefore, there is a high interest in the development of technologies that allow control over PC formation, as this would provide a handle to manipulate NPs in biological fluids. We present a strategy that enables the reversible disruption of the PC using external stimuli, thereby allowing a precise regulation of NP cellular uptake. The approach, demonstrated for gold nanoparticles (AuNPs), is based on a biorthogonal, supramolecular host-guest interactions between an anionic dye bound to the AuNP surface and a positively charged macromolecular cage. This supramolecular complex effectively behaves as a zwitterionic NP ligand, which is able not only to prevent PC formation but also to disrupt a previously formed hard corona. With this supramolecular stimulus, the cellular internalization of AuNPs can be enhanced by up to 30-fold in some cases, and even NP cellular uptake in phagocytic cells can be regulated. Additionally, we demonstrate that the conditional cell uptake of purposely designed gold nanorods can be used to selectively enhance photothermal cell death.

Original languageEnglish
Pages (from-to)5382-5391
Number of pages10
JournalACS Nano
Issue number5
Early online date27 Feb 2020
Publication statusPublished - 26 May 2020


  • cellular uptake
  • gold nanoparticles
  • host-guest chemistry
  • photothermal therapy
  • protein corona


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