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Quantification of monodisperse and biocompatible gold nanoparticles by single-particle ICP-MS

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Abstract

Bioanalytical and biomedical applications often require nanoparticles that exhibit narrow size distributions and biocompatibility. Here, we demonstrate how different synthesis methods affect gold nanoparticle (AuNPs) monodispersity and cytotoxicity. Using single particle inductively coupled plasma mass spectrometry (SP-ICP-MS), we found that the size distribution of AuNPs synthesized with a cetyltrimethylammonium chloride (CTAC) cap was significantly improved compared to AuNPs synthesized with citrate cap** agents. We determined an up to 4× decrease in the full width at half maximum (FWHM) value of the normal distributions of AuNP diameter and up to a 12% decrease in relative standard deviation (RSD). While the CTAC-capped AuNPs exhibit narrow nanoparticle size distributions, they are cytotoxic, which limits safe and effective bioanalytical and biomedical applications. We sought to impart biocompatibility to CTAC-capped AuNPs through a PEGylation-based surface ligand exchange. We developed a unique ligand exchange method driven by physical force. We demonstrated the successful PEGylation using various PEG derivatives and used these PEGylated nanoparticles to further bioconjugate nucleic acids and peptides. Using cell viability quantification, we confirmed that the monodisperse PEGylated AuNPs were biocompatible. Our monodisperse and biocompatible nanoparticles may advance safe and effective bioanalytical and biomedical applications of nanomaterials.

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Acknowledgements

The authors acknowledge the assistance of Dr. Steven Foster, Dr. Preston Larson, Dr. Julian Sabisch, and Dr. Ben Fowler. Additionally, the authors acknowledge the University of Oklahoma (OU) Samuel Roberts Noble Microscopy Laboratory (SRNML), the OU Mass Spectrometry, Proteomics & Metabolomics (MSPM) Core, and the Oklahoma Medical Research Foundation (OMRF) Imaging Core Facility for assistance. The authors would like to thank Sarah Butterfield, Majood Haddad, Luke Whitehead, Nathan Mjema, Abigail Thomas, and Sam Ferguson for their help synthesizing nanoparticles.

Funding

This work was supported in part by awards from NIH COBRE (P20GM135009), NSF CAREER (2048130), and OCAST (HR20-106) and by the University of Oklahoma Vice President for Research and Partnerships SRNML Voucher Program.

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  1. Alex N. Frickenstein and Shirsha Mukherjee contributed equally to this work.

Authors and Affiliations

  1. Stephenson School of Biomedical Engineering, University of Oklahoma, Norman, OK, 73019, USA

    Alex N. Frickenstein, Shirsha Mukherjee, Tekena Harcourt, Yuxin He, Vinit Sheth, Lin Wang, Zain Malik & Stefan Wilhelm

  2. Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA

    Stefan Wilhelm

  3. Institute for Biomedical Engineering, Science, and Technology (IBEST), University of Oklahoma, Norman, OK, 73019, USA

    Stefan Wilhelm

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  1. Alex N. Frickenstein
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Published in the topical collection Young Investigators in (Bio-)Analytical Chemistry 2023 with guest editors Zhi-Yuan Gu, Beatriz Jurado-Sánchez, Thomas H. Linz, Leandro Wang Hantao, Nongnoot Wongkaew, and Peng Wu.

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Frickenstein, A.N., Mukherjee, S., Harcourt, T. et al. Quantification of monodisperse and biocompatible gold nanoparticles by single-particle ICP-MS. Anal Bioanal Chem 415, 4353–4366 (2023). https://doi.org/10.1007/s00216-023-04540-x

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