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Two-dimensional (2D) nanosheets have emerged as an important class of nanomaterial with great potential in the field of biomedicines, particularly in cancer theranostics. However, owing to the lack of effective methods that synthesize uniform 2D nanomaterials with controlled size, systematic evaluation of size-dependent bio-behaviors of 2D nanomaterials is rarely reported. To the best of our knowledge, we are the first to report a systematic evaluation of the influence of size of 2D nanomaterials on their bio-behaviors. 2D Pd nanosheets with diameters ranging from 5 to 80 nm were synthesized and tested in cell and animal models to assess their size-dependent bioapplication, biodistribution, elimination, toxicity, and genomic gene expression profiles. Our results showed size significantly influences the biological behaviors of Pd nanosheets, including their photothermal and photoacoustic effects, pharmacokinetics, and toxicity. Compared to larger-sized Pd nanosheets, smaller-sized Pd nanosheets exhibited more advanced photoacoustic imaging and photothermal effects upon ultralow laser irradiation. Moreover, in vivo results indicated that 5-nm Pd nanosheets escape from the reticuloendothelial system with a longer blood half-life and can be cleared by renal excretion, while Pd nanosheets with larger sizes mainly accumulate in the liver and spleen. The 30-nm Pd nanosheets exhibited the highest tumor accumulation. Although Pd nanosheets did not cause any appreciable toxicity at the cellular level, we observed slight lipid accumulation in the liver and inflammation in the spleen. Genomic gene expression analysis showed that 80-nm Pd nanosheets interacted with more cellular components and affected more biological processes in the liver, as compared to 5-nm Pd nanosheets. We believe this work will provide valuable information and insights into the clinical application of 2D Pd nanosheets as nanomedicines.


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Safety profile of two-dimensional Pd nanosheets for photothermal therapy and photoacoustic imaging

Show Author's information Mei Chen1,§Shuzhen Chen2,3,§Chengyong He2,§Shiguang Mo1Xiaoyong Wang2Gang Liu2( )Nanfeng Zheng1( )
State Key Laboratory for Physical Chemistry of Solid SurfacesCollaborative Innovation Center of Chemistry for Energy Materials, and Engineering Research Center for Nano-Preparation Technology of Fujian ProvinceCollege of Chemistry and Chemical Engineering, Xiamen UniversityXiamen361005China
State Key Laboratory of Molecular Vaccinology and Molecular DiagnosticsCenter for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen UniversityXiamen361005China
Department of Microbiology and ImmunologyXiamen Medical CollegeXiamen361008China

§ These authors contributed equally to this work.

Abstract

Two-dimensional (2D) nanosheets have emerged as an important class of nanomaterial with great potential in the field of biomedicines, particularly in cancer theranostics. However, owing to the lack of effective methods that synthesize uniform 2D nanomaterials with controlled size, systematic evaluation of size-dependent bio-behaviors of 2D nanomaterials is rarely reported. To the best of our knowledge, we are the first to report a systematic evaluation of the influence of size of 2D nanomaterials on their bio-behaviors. 2D Pd nanosheets with diameters ranging from 5 to 80 nm were synthesized and tested in cell and animal models to assess their size-dependent bioapplication, biodistribution, elimination, toxicity, and genomic gene expression profiles. Our results showed size significantly influences the biological behaviors of Pd nanosheets, including their photothermal and photoacoustic effects, pharmacokinetics, and toxicity. Compared to larger-sized Pd nanosheets, smaller-sized Pd nanosheets exhibited more advanced photoacoustic imaging and photothermal effects upon ultralow laser irradiation. Moreover, in vivo results indicated that 5-nm Pd nanosheets escape from the reticuloendothelial system with a longer blood half-life and can be cleared by renal excretion, while Pd nanosheets with larger sizes mainly accumulate in the liver and spleen. The 30-nm Pd nanosheets exhibited the highest tumor accumulation. Although Pd nanosheets did not cause any appreciable toxicity at the cellular level, we observed slight lipid accumulation in the liver and inflammation in the spleen. Genomic gene expression analysis showed that 80-nm Pd nanosheets interacted with more cellular components and affected more biological processes in the liver, as compared to 5-nm Pd nanosheets. We believe this work will provide valuable information and insights into the clinical application of 2D Pd nanosheets as nanomedicines.

Keywords: photoacoustic imaging, photothermal therapy, Pd nanosheets, toxicity evaluation, genomic gene expression

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Publication history
Copyright
Acknowledgements

Publication history

Received: 31 August 2016
Revised: 20 October 2016
Accepted: 28 October 2016
Published: 06 December 2016
Issue date: April 2017

Copyright

© Tsinghua University Press and Springer-Verlag Berlin Heidelberg 2016

Acknowledgements

Acknowledgements

This work was supported by the National Basic Research Program of China (Nos. 2014CB932004 and 2015CB932303) and the National Natural Science Foundation of China (Nos. 21420102001, 21131005 and 81422023).

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