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The influence of physiological environment on the targeting effect of aptamer-guided gold nanoparticles

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Abstract

Aptamer guided nanomedicine shows great promise in targeted cancer therapies. However the loss of targeting capacity during in vivo or clinical trials has largely hindered its popularity and there are no systematic studies to elucidate the causes. Herein, we investigated such loss of targeting capacity by examining how the physiological milieu affected targeting effect. Aptamer functionalized gold nanoparticle (AuNP) was chosen as the model and exposed to human blood serum that is used to mimic physiological milieu. Dynamic light scattering (DLS), flow cytometry and label-free liquid chromatography tandem mass spectrometry (LC-MS/MS) were employed to determine variations of NPs’ surface chemistry and biological identities changes after serum exposure. Results showed that the targeting ability loss was caused by protein corona blocking, replacement and enzymatic cleavage of surface aptamer targeting ligands. Noteworthy, the aggregation issue is critical for the smaller NPs. Analysis of the protein corona profile indicated the accumulation of immune-related proteins on the surface of aptamer-conjugated NPs, which could induce immune response, resulting in rapid clearance of NPs.

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Acknowledgements

We would like to acknowledge Dr. Yanyan Lin at The First Hospital of Lanzhou University for donation of blood samples. We would also like to thank Dr. Jianglin Li for performing LC-MS/MS. This work was financially supported by the National Natural Science Foundation of China (Nos. 21522501, 21521063 and 61673405), Hunan Provincial Natural Science Foundation of China (No. 2018JJ1007), and the Science and Technology Development Fund of Macao S.A.R (FDCT, 097/2015/A3).

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Author notes

  1. Ding Ding

    Present address: Present address: Institute of Molecular Medicine, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, Shanghai, 200240, China

Authors and Affiliations

  1. Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering and College of Life Sciences, Hunan University, Changsha, 410082, China

    Ding Ding, Yinling Zhang, Zhuo Chen & Weihong Tan

  2. School of Medicine, Queen’s University, 81 Barrie Street, Kingston, ON, K7L 3N6, Canada

    Edward A. Sykes

  3. Faculty of Science and Technology, University of Macau, Avenida da Universidade, Macau Taipa, 999078, China

    Long Chen

  4. Department of Chemistry, Departments of Physiology and Functional Genomics, Center for Research at the Bio/Nano Interface, UF Health Cancer Center, UF Genetics Institute and McKnight Brain Institute, University of Florida, Gainesville, Florida, 32611, USA

    Weihong Tan

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  1. Ding Ding
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Correspondence to Zhuo Chen or Weihong Tan.

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Ding, D., Zhang, Y., Sykes, E.A. et al. The influence of physiological environment on the targeting effect of aptamer-guided gold nanoparticles. Nano Res. 12, 129–135 (2019). https://doi.org/10.1007/s12274-018-2191-9

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  • DOI: https://doi.org/10.1007/s12274-018-2191-9

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