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Orthogonal analysis of functional gold nanoparticles for biomedical applications

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Abstract

We report a comprehensive strategy based on implementation of orthogonal measurement techniques to provide critical and verifiable material characteristics for functionalized gold nanoparticles (AuNPs) used in biomedical applications. Samples were analyzed before and after ≈50 months of cold storage (≈4 °C). Biomedical applications require long-term storage at cold temperatures, which could have an impact on AuNP therapeutics. Thiolated polyethylene glycol (SH-PEG)-conjugated AuNPs with different terminal groups (methyl-, carboxylic-, and amine-) were chosen as a model system due to their high relevancy in biomedical applications. Electrospray-differential mobility analysis, asymmetric-flow field flow fractionation, transmission electron microscopy, scanning electron microscopy, atomic force microscopy, inductively coupled plasma mass spectrometry, and small-angle X-ray scattering were employed to provide both complementary and orthogonal information on (1) particle size and size distribution, (2) particle concentrations, (3) molecular conjugation properties (i.e., conformation and surface packing density), and (4) colloidal stability. Results show that SH-PEGs were conjugated on the surface of AuNPs to form a brush-like polymer corona. The surface packing density of SH-PEG was ≈0.42 nm−2 for the methyl-PEG-SH AuNPs, ≈0.26 nm−2 for the amine-SH-PEG AuNPs, and ≈0.18 nm−2 for the carboxylic-PEG-SH AuNPs before cold storage, approximately 10 % of its theoretical maximum value. The conformation of surface-bound SH-PEGs was then estimated to be in an intermediate state between brush-like and random-coiled, based on the measured thicknesses in liquid and in dry states. By analyzing the change in particle size distribution and number concentration in suspension following cold storage, the long term colloidal stability of AuNPs was shown to be significantly improved via functionalization with SH-PEG, especially in the case of methyl-PEG-SH and carboxylic-PEG-SH (i.e., we estimate that >80 % of SH-PEG5K remained on the surface of AuNPs during storage). The work described here provides a generic strategy to track and analyze the material properties of functional AuNPs intended for biomedical applications, and highlights the importance of a multi-technique analysis. The effects of long term storage on the physical state of the particles, and on the stability of the ligand-AuNP conjugates, are employed to demonstrate the capacity of this approach to address critical issues relevant to clinical applications.

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Acknowledgments

The authors thank Katherine Tyner at the U.S. Food and Drug Administration, Center for Drug Evaluation and Research, for providing test samples used in this study and for helpful comments. The authors also thank Hsiao-Fang Wang and Rong-Ming Ho at NTHU for assistance in TEM. DHT and YFL thank the Ministry of Science and Technology of the Republic of China (Taiwan), for financial support of this research under Contract no. Grant NSC102-2218-E-007-015-MY2.

Use of the Advanced Photon Source, an Office of Science User Facility operated for the U.S. Department of Energy (DOE) Office of Science by Argonne National Laboratory, was supported by the U.S. DOE under Contract No. DE-AC02-06CH11357. ChemMatCARS Sector 15 is principally supported by the Divisions of Chemistry (CHE) and Materials Research (DMR), National Science Foundation, under grant number NSF/CHE-1346572.

Conflict of interest

The authors declare no conflict of interest.

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Authors and Affiliations

  1. Materials Measurement Science Division, National Institute of Standards and Technology, Gaithersburg, MD, 20899, USA

    De-Hao Tsai, Frank W. DelRio, Tae Joon Cho, Fan Zhang, Andrew Allen & Vincent A. Hackley

  2. Department of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan, Republic of China

    De-Hao Tsai & Yi-Fu Lu

  3. Chemical Sciences Division, National Institute of Standards and Technology, Gaithersburg, MD, 20899, USA

    Suvajyoti Guha & Michael R. Zachariah

  4. Departments of Chemical Engineering and Chemistry, University of Maryland, College Park, MD, 20740, USA

    Michael R. Zachariah

Authors
  1. De-Hao Tsai
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  2. Yi-Fu Lu
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  7. Fan Zhang
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  9. Vincent A. Hackley
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Correspondence to De-Hao Tsai or Vincent A. Hackley.

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Tsai, DH., Lu, YF., DelRio, F.W. et al. Orthogonal analysis of functional gold nanoparticles for biomedical applications. Anal Bioanal Chem 407, 8411–8422 (2015). https://doi.org/10.1007/s00216-015-9011-9

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  • DOI: https://doi.org/10.1007/s00216-015-9011-9

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