RT Journal Article T1 Reversible Control of Protein Corona Formation on Gold Nanoparticles Using Host–Guest Interactions A1 Mosquera Mosquera, Jesús A1 García, Isabel A1 Henriksen-Lacey, Malou A1 Martínez-Calvo, Miguel A1 Dhanjani, Mónica A1 Mascareñas Cid, José Luis A1 Liz-Marzán, Luis M. K1 Cell uptake K1 Metal nanoparticles K1 Gold K1 Colloids K1 Assays K1 Protein corona K1 Gold nanoparticles K1 Host−guest chemistry K1 Cellular uptake K1 Photothermal therapy AB 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 PB ACS Publications SN 1936-0851 YR 2020 FD 2020 LK http://hdl.handle.net/10347/22786 UL http://hdl.handle.net/10347/22786 LA eng NO ACS Nano 2020, 14, 5, 5382–5391 NO Funding was received from MINECO (SAF2016-76689-R, MAT2017-86659-R), Xunta de Galicia (2015-CP082, ED431C 2017/19, Centro singular de investigación de Galicia accreditation 2019-2022, ED431G 2019/03), the European Union (European Regional Development Fund), and the European Research Council (ERC AdG No. 787510 to L.M.L.-M.; ERC AdG No. 340055 to J.L.M). J.M. and M.M.-C. thank MINECO for Juan de la Cierva fellowships (FJCI-2015-25080 and IJCI-2014-19326). The proteomic analysis was performed in the proteomics platform at CIC bioGUNE, which is supported by Basque Department of Industry, Tourism and Trade (Etortek and Elkartek programs), the Innovation Technology Department of the Bizkaia County; The ProteoRed-ISCIII (Grant No. PRB3 IPT17/0019); CIBERehd Network, and Severo Ochoa Grant (No. SEV-2016-0644). This work was performed under the Maria de Maeztu Units of Excellence Program from the Spanish State Research Agency, Grant No. MDM-2017-0720 DS Minerva RD 28 abr 2026