Limiting the protein corona: A successful strategy for in vivo active targeting of anti-HER2 nanobody-functionalized nanostars.
Gold nanoparticles hold great promise as anti-cancer theranostic agents against cancer by actively targeting the tumor cells. As this potential has been supported numerously during in vitro experiments, the effective application is hampered by our limited understanding and control of the interactions within complex in vivo biological systems. When these nanoparticles are exposed to a biological environment, their surfaces become covered with proteins and biomolecules, referred to as the protein corona, reducing the active targeting capabilities. We demonstrate a chemical strategy to overcome this issue by reducing the protein corona's thickness by blocking the active groups of the self-assembled monolayer on gold nanostars. An optimal blocking agent, 2-mercapto ethanol, has been selected based on charge and length of the carbon chain. By using a nanobody as a biological ligand of the human epidermal growth factor 2 receptor (HER2), the active targeting is demonstrated in vitro and in vivo in an experimental tumor model by using darkfield microscopy and photoacoustic imaging. In this study, we have established gold nanostars as a conceivable theranostic agent with a specificity for HER2-positive tumors.
Department of Life Science Technology, Imec, Kapeldreef 75, 3001, Leuven, Belgium; Faculty of Medicine, Department of Imaging and Pathology, Biomedical MRI Unit, KU Leuven, O&N 1, Herestraat 49, 3000, Leuven, Belgium; Faculty of Medicine, Molecular Small Animal Imaging Center (MoSAIC), KU Leuven, O&N 1, Herestraat 49, 3000, Leuven, Belgium. Electronic address: antoinedhollander@hotmail.com.
Antoine
A
D'Hollander
Department of Life Science Technology, Imec, Kapeldreef 75, 3001, Leuven, Belgium.
Hilde
H
Jans
Faculty of Medicine, Department of Imaging and Pathology, Biomedical MRI Unit, KU Leuven, O&N 1, Herestraat 49, 3000, Leuven, Belgium; Faculty of Medicine, Molecular Small Animal Imaging Center (MoSAIC), KU Leuven, O&N 1, Herestraat 49, 3000, Leuven, Belgium.
Greetje Vande
GV
Velde
Department of Life Science Technology, Imec, Kapeldreef 75, 3001, Leuven, Belgium.
Charlotte
C
Verstraete
In Vivo Cellular and Molecular Imaging Laboratory, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103 Building K, 1090, Brussels, Belgium; Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel (VUB), Pleinlaan 2 Building E, 1050, Brussels, Belgium.
Sam
S
Massa
In Vivo Cellular and Molecular Imaging Laboratory, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103 Building K, 1090, Brussels, Belgium; Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel (VUB), Pleinlaan 2 Building E, 1050, Brussels, Belgium.
Nick
N
Devoogdt
Department of Life Science Technology, Imec, Kapeldreef 75, 3001, Leuven, Belgium.
Tim
T
Stakenborg
Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel (VUB), Pleinlaan 2 Building E, 1050, Brussels, Belgium.
Serge
S
Muyldermans
Department of Life Science Technology, Imec, Kapeldreef 75, 3001, Leuven, Belgium.
Liesbet
L
Lagae
Faculty of Medicine, Department of Imaging and Pathology, Biomedical MRI Unit, KU Leuven, O&N 1, Herestraat 49, 3000, Leuven, Belgium; Faculty of Medicine, Molecular Small Animal Imaging Center (MoSAIC), KU Leuven, O&N 1, Herestraat 49, 3000, Leuven, Belgium.
Uwe
U
Himmelreich
D000818:Animals; D016466:CHO Cells; D045744:Cell Line, Tumor; D003412:Cricetulus; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D006046:Gold / Q000737:chemistry; D006801:Humans; D008623:Mercaptoethanol / Q000737:chemistry*; D053768:Metal Nanoparticles / Q000737:chemistry; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D000066970:Protein Corona / Q000737:chemistry*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology*; D061905:Single-Domain Antibodies / Q000737:chemistry* / Q000276:immunology* / Q000648:ultrastructure; D000068936:Theranostic Nanomedicine / Q000379:methods; D016896:Treatment Outcome
D006046:Gold; D008623:Mercaptoethanol; D000066970:Protein Corona; D018719:Erb-b2 Receptor Tyrosine Kinases; D061905:Single-Domain Antibodies; C508053:ERBB2 protein, human
Active targeting; Gold nanostars; Nanobody; Photoacoustic imaging; Protein corona