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Article

Selective Integrin α5β1 Targeting through Spatially Constrained Multivalent DNA-Based Nanoparticles

1
Programmable Biomaterials Laboratory, Institute of Materials, School of Engineering, Ecole Polytechnique Fédérale Lausanne, 1015 Lausanne, Switzerland
2
Interfaculty Bioengineering Institute, School of Engineering, Ecole Polytechnique Fédérale Lausanne, 1015 Lausanne, Switzerland
*
Author to whom correspondence should be addressed.
Academic Editors: Adrian Keller and Veikko Linko
Molecules 2022, 27(15), 4968; https://doi.org/10.3390/molecules27154968
Received: 30 June 2022 / Revised: 29 July 2022 / Accepted: 2 August 2022 / Published: 4 August 2022
(This article belongs to the Special Issue DNA Nanostructures at Surfaces)
Targeting cells specifically based on receptor expression levels remains an area of active research to date. Selective binding of receptors cannot be achieved by increasing the individual binding strength, as this does not account for differing distributions of receptor density across healthy and diseased cells. Engaging receptors above a threshold concentration would be desirable in devising selective diagnostics. Integrins are prime target candidates as they are readily available on the cell surface and have been reported to be overexpressed in diseases. Insights into their spatial organization would therefore be advantageous to design selective targeting agents. Here, we investigated the effect of activation method on integrin α5β1 clustering by immunofluorescence and modeled the global neighbor distances with input from an immuno-staining assay and image processing of microscopy images. This data was used to engineer spatially-controlled DNA-scaffolded bivalent ligands, which we used to compare trends in spatial-selective binding observed across HUVEC, CHO and HeLa in resting versus activated conditions in confocal microscopy images. For HUVEC and CHO, the data demonstrated an improved selectivity and localisation of binding for smaller spacings ~7 nm and ~24 nm, in good agreement with the model. A deviation from the mode predictions for HeLa was observed, indicative of a clustered, instead of homogeneous, integrin organization. Our findings demonstrate how low-technology imaging methods can guide the design of spatially controlled ligands to selectively differentiate between cell type and integrin activation state. View Full-Text
Keywords: selective targeting; spatial tolerance; DNA nanotechnology; integrins; multivalency selective targeting; spatial tolerance; DNA nanotechnology; integrins; multivalency
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MDPI and ACS Style

Kurisinkal, E.E.; Caroprese, V.; Koga, M.M.; Morzy, D.; Bastings, M.M.C. Selective Integrin α5β1 Targeting through Spatially Constrained Multivalent DNA-Based Nanoparticles. Molecules 2022, 27, 4968. https://doi.org/10.3390/molecules27154968

AMA Style

Kurisinkal EE, Caroprese V, Koga MM, Morzy D, Bastings MMC. Selective Integrin α5β1 Targeting through Spatially Constrained Multivalent DNA-Based Nanoparticles. Molecules. 2022; 27(15):4968. https://doi.org/10.3390/molecules27154968

Chicago/Turabian Style

Kurisinkal, Eva E., Vincenzo Caroprese, Marianna M. Koga, Diana Morzy, and Maartje M. C. Bastings. 2022. "Selective Integrin α5β1 Targeting through Spatially Constrained Multivalent DNA-Based Nanoparticles" Molecules 27, no. 15: 4968. https://doi.org/10.3390/molecules27154968

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