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Theranostic nanoparticles are integrated systems useful for simultaneous diagnosis and imaging guided delivery of therapeutic drugs, with wide ranging potential applications in the clinic. Here we developed a theranostic nanoparticle (~ 24 nm size by dynamic light scattering) p-FE-PTX-FA based on polymeric micelle encapsulating an organic dye (FE) fluorescing in the 1, 000–1, 700 nm second near-infrared (NIR-II) window and an anti-cancer drug paclitaxel. Folic acid (FA) was conjugated to the nanoparticles to afford specific binding to molecular folate receptors on murine breast cancer 4T1 tumor cells. In vivo, the nanoparticles accumulated in 4T1 tumor through both passive and active targeting effect. Under an 808 nm laser excitation, fluorescence detection above 1, 300 nm afforded a large Stokes shift, allowing targeted molecular imaging tumor with high signal to background ratios, reaching a high tumor to normal tissue signal ratio (T/NT) of (20.0 ± 2.3). Further, 4T1 tumors on mice were completed eradicated by paclitaxel released from p-FE-PTA-FA within 20 days of the first injection. Pharmacokinetics and histology studies indicated p-FE-PTX-FA had no obvious toxic side effects to major organs. This represented the first NIR-II theranostic agent developed.


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A theranostic agent for cancer therapy and imaging in the second nearinfrared window

Show Author's information Zhuoran Ma1,§Hao Wan1,§Weizhi Wang2,§Xiaodong Zhang3Takaaki Uno4Qianglai Yang5Jingying Yue1Hongpeng Gao1Yeteng Zhong1Ye Tian1Qinchao Sun1Yongye Liang5Hongjie Dai1( )
,Department of Chemistry, Stanford University,Stanford, CA,94305,USA;
CAS Key Laboratory of Standardization and Measurement for Nanotechnology,CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China,Beijing,100190,China;
Department of Physics and Tianjin Key Laboratory of Low Dimensional Materials Physics and Preparing Technology,School of Sciences, Tianjin University,Tianjin,300350,China;
JSR Corporation Advanced Materials Research Laboratories, 100 Kawajiri-Cho,Yokkaichi, Mie,5108552,Japan;
Department of Materials Science and Engineering,South University of Science and Technology of China,Shenzhen,518055,China;

§Zhuoran Ma, Hao Wan, Weizhi Wang, and Xiaodong Zhang contributed equally to this work.

Abstract

Theranostic nanoparticles are integrated systems useful for simultaneous diagnosis and imaging guided delivery of therapeutic drugs, with wide ranging potential applications in the clinic. Here we developed a theranostic nanoparticle (~ 24 nm size by dynamic light scattering) p-FE-PTX-FA based on polymeric micelle encapsulating an organic dye (FE) fluorescing in the 1, 000–1, 700 nm second near-infrared (NIR-II) window and an anti-cancer drug paclitaxel. Folic acid (FA) was conjugated to the nanoparticles to afford specific binding to molecular folate receptors on murine breast cancer 4T1 tumor cells. In vivo, the nanoparticles accumulated in 4T1 tumor through both passive and active targeting effect. Under an 808 nm laser excitation, fluorescence detection above 1, 300 nm afforded a large Stokes shift, allowing targeted molecular imaging tumor with high signal to background ratios, reaching a high tumor to normal tissue signal ratio (T/NT) of (20.0 ± 2.3). Further, 4T1 tumors on mice were completed eradicated by paclitaxel released from p-FE-PTA-FA within 20 days of the first injection. Pharmacokinetics and histology studies indicated p-FE-PTX-FA had no obvious toxic side effects to major organs. This represented the first NIR-II theranostic agent developed.

Keywords: fluorescence imaging, cancer therapy, second near-infrared window, theranostic nanoparticles

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Publication history
Copyright
Acknowledgements

Publication history

Received: 24 July 2018
Revised: 18 September 2018
Accepted: 18 September 2018
Published: 29 September 2018
Issue date: February 2019

Copyright

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

Acknowledgements

Acknowledgements

This study was supported by National Institutes of Health NIH DP1-NS-105737, the Deng family gift, and the Shenzhen Peacock Program Grant KQTD20140630160825828.

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