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A Single-Molecule View at Nanoparticle Targeting Selectivity: Correlating Ligand Functionality and Cell Receptor Density
[Image: see text] Antibody-functionalized nanoparticles (NPs) are commonly used to increase the targeting selectivity toward cells of interest. At a molecular level, the number of functional antibodies on the NP surface and the density of receptors on the target cell determine the targeting interact...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8945370/ https://www.ncbi.nlm.nih.gov/pubmed/35274534 http://dx.doi.org/10.1021/acsnano.1c08277 |
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author | Woythe, Laura Madhikar, Pranav Feiner-Gracia, Natalia Storm, Cornelis Albertazzi, Lorenzo |
author_facet | Woythe, Laura Madhikar, Pranav Feiner-Gracia, Natalia Storm, Cornelis Albertazzi, Lorenzo |
author_sort | Woythe, Laura |
collection | PubMed |
description | [Image: see text] Antibody-functionalized nanoparticles (NPs) are commonly used to increase the targeting selectivity toward cells of interest. At a molecular level, the number of functional antibodies on the NP surface and the density of receptors on the target cell determine the targeting interaction. To rationally develop selective NPs, the single-molecule quantitation of both parameters is highly desirable. However, techniques able to count molecules with a nanometric resolution are scarce. Here, we developed a labeling approach to quantify the number of functional cetuximabs conjugated to NPs and the expression of epidermal growth factor receptors (EGFRs) in breast cancer cells using direct stochastic optical reconstruction microscopy (dSTORM). The single-molecule resolution of dSTORM allows quantifying molecules at the nanoscale, giving a detailed insight into the distributions of individual NP ligands and cell receptors. Additionally, we predicted the fraction of accessible antibody-conjugated NPs using a geometrical model, showing that the total number exceeds the accessible number of antibodies. Finally, we correlated the NP functionality, cell receptor density, and NP uptake to identify the highest cell uptake selectivity regimes. We conclude that single-molecule functionality mapping using dSTORM provides a molecular understanding of NP targeting, aiding the rational design of selective nanomedicines. |
format | Online Article Text |
id | pubmed-8945370 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-89453702022-03-28 A Single-Molecule View at Nanoparticle Targeting Selectivity: Correlating Ligand Functionality and Cell Receptor Density Woythe, Laura Madhikar, Pranav Feiner-Gracia, Natalia Storm, Cornelis Albertazzi, Lorenzo ACS Nano [Image: see text] Antibody-functionalized nanoparticles (NPs) are commonly used to increase the targeting selectivity toward cells of interest. At a molecular level, the number of functional antibodies on the NP surface and the density of receptors on the target cell determine the targeting interaction. To rationally develop selective NPs, the single-molecule quantitation of both parameters is highly desirable. However, techniques able to count molecules with a nanometric resolution are scarce. Here, we developed a labeling approach to quantify the number of functional cetuximabs conjugated to NPs and the expression of epidermal growth factor receptors (EGFRs) in breast cancer cells using direct stochastic optical reconstruction microscopy (dSTORM). The single-molecule resolution of dSTORM allows quantifying molecules at the nanoscale, giving a detailed insight into the distributions of individual NP ligands and cell receptors. Additionally, we predicted the fraction of accessible antibody-conjugated NPs using a geometrical model, showing that the total number exceeds the accessible number of antibodies. Finally, we correlated the NP functionality, cell receptor density, and NP uptake to identify the highest cell uptake selectivity regimes. We conclude that single-molecule functionality mapping using dSTORM provides a molecular understanding of NP targeting, aiding the rational design of selective nanomedicines. American Chemical Society 2022-03-11 2022-03-22 /pmc/articles/PMC8945370/ /pubmed/35274534 http://dx.doi.org/10.1021/acsnano.1c08277 Text en © 2022 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Woythe, Laura Madhikar, Pranav Feiner-Gracia, Natalia Storm, Cornelis Albertazzi, Lorenzo A Single-Molecule View at Nanoparticle Targeting Selectivity: Correlating Ligand Functionality and Cell Receptor Density |
title | A
Single-Molecule View at Nanoparticle Targeting Selectivity:
Correlating Ligand Functionality and Cell Receptor Density |
title_full | A
Single-Molecule View at Nanoparticle Targeting Selectivity:
Correlating Ligand Functionality and Cell Receptor Density |
title_fullStr | A
Single-Molecule View at Nanoparticle Targeting Selectivity:
Correlating Ligand Functionality and Cell Receptor Density |
title_full_unstemmed | A
Single-Molecule View at Nanoparticle Targeting Selectivity:
Correlating Ligand Functionality and Cell Receptor Density |
title_short | A
Single-Molecule View at Nanoparticle Targeting Selectivity:
Correlating Ligand Functionality and Cell Receptor Density |
title_sort | a
single-molecule view at nanoparticle targeting selectivity:
correlating ligand functionality and cell receptor density |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8945370/ https://www.ncbi.nlm.nih.gov/pubmed/35274534 http://dx.doi.org/10.1021/acsnano.1c08277 |
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