期刊
ACS NANO
卷 16, 期 3, 页码 3785-3796出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.1c08277
关键词
nanomedicine; active targeting dSTORM; heterogeneity; nanoparticle functionality; super-resolution microscopy
类别
资金
- European Research Council [ERCStG-757397]
- Netherlands Organization for Scientific Research (NOW VIDI Grant) [192.028]
- Open Technology Program 'BioMonitor' from the Engineering and Applied Sciences division of NWO, the Dutch Science Council
This study developed a labeling approach using dSTORM to accurately quantify the number of functional antibodies on the surface of nanoparticles and the density of receptors on target cells. The single-molecule resolution of dSTORM provided detailed insights into the distribution of ligands and receptors. Furthermore, the study identified the highest cell uptake selectivity regimes by correlating nanoparticle functionality, cell receptor density, and nanoparticle uptake.
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.
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