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Nano Research 2019, 12(1): 129-135 https://doi.org/10.1007/s12274-018-2191-9
Research Article | Issue | Published: 17 September 2018

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

Show Author's Information Ding Ding1,†,  Yinling Zhang1,  Edward A. Sykes2,  Long Chen3,  Zhuo Chen1( ),  Weihong Tan1,4( )
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;
School of Medicine, Queenos University, 81 Barrie Street, Kingston, ON, ON, K7L 3N6, Canada;
Faculty of Science and Technology,University of Macau, Avenida da Universidade,Macau Taipa,999078,China;
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

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

Keywords:
nanomedicine, aptamer, targeting effect, physiological environment
Topics:
Gold nanoparticlesMass spectrometryMedical nanotechnologyMetal nanoparticlesPhysiologyProteins
Cite this article:
Ding D, Zhang Y, Sykes EA, et al. The influence of physiological environment on the targeting effect of aptamer-guided gold nanoparticles. Nano Research, 2019, 12(1): 129-135. https://doi.org/10.1007/s12274-018-2191-9
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Abstract Full text Electronic supplementary material About this article

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 NPso 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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Electronic supplementary material
About this article

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

Show Author's information Ding Ding1,†, Yinling Zhang1, Edward A. Sykes2, Long Chen3, Zhuo Chen1( ), Weihong Tan1,4( )
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;
School of Medicine, Queenos University, 81 Barrie Street, Kingston, ON, ON, K7L 3N6, Canada;
Faculty of Science and Technology,University of Macau, Avenida da Universidade,Macau Taipa,999078,China;
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

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

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 NPso 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.

Keywords: nanomedicine, aptamer, targeting effect, physiological environment

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Publication history
Copyright
Acknowledgements

Publication history

Received: 01 July 2018
Revised: 24 August 2018
Accepted: 02 September 2018
Published: 17 September 2018
Issue date: January 2019

Copyright

© Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature 2018

Acknowledgements

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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