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As a new type of cancer treatment, photoacoustic (PA) therapy is based on PA shockwave for rapid, selective and effective killing of cancer cells. The nucleus has been widely used as a target for tumor therapy, which has obtained a very considerable therapeutic effect. In situ destruction of tumor cell nucleus by photoacoustic therapy has not been studied. In this paper, a highly efficient nucleus-targeted photoacoustic theranostic polymer was developed for fluorescence and photoacoustic dual-mode imaging-guided PA therapy. The prepared polymer consists of nucleus targeting TAT peptide (TAT: YGRKKRRQRRR), hydrophilic chain poly (N,N-dimethylacrylamide) (PDMA), and near-infrared (NIR) light absorbing agent (hCyR), which can self-assemble to form nanoparticles of approximately 28 nm (denoted as TAT-PDMA-hCyR NPs). The designed nanoparticles show excellent nucleus targeting and tumor cell death (up to 80%) caused by DNA damage under pulsed laser irradiation compared to non-nucleus target counterpart PDMA-hCyR NPs without TAT peptide in vitro. As expected, the fluorescence and PA dual-mode imaging observed that TAT-PDMA-hCyR NPs were able to passively target and enrich in tumors, providing an experimental basis for in vivo treatment and thus ensuring a significant tumor inhibition rate (about 92%). In conclusion, this study provides a new and practicable method for the development of nucleus-targeting nanoparticles as potential theranostic agent for in vivo cancer imaging and therapy.


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Specific photoacoustic cavitation through nucleus targeted nanoparticles for high-efficiency tumor therapy

Show Author's information Yuan Wang1,2,§Guangle Niu3,4,§Shaodong Zhai1,2Wenjia Zhang1,2Da Xing1,2( )
MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, South China Normal University, Guangzhou 510631, China
College of Biophotonics, South China Normal University, Guangzhou 510631, China
Key Laboratory of Photochemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190, China
Department of Pharmacology & Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China

§ Yuan Wang and Guangle Niu contributed equally to this work.

Abstract

As a new type of cancer treatment, photoacoustic (PA) therapy is based on PA shockwave for rapid, selective and effective killing of cancer cells. The nucleus has been widely used as a target for tumor therapy, which has obtained a very considerable therapeutic effect. In situ destruction of tumor cell nucleus by photoacoustic therapy has not been studied. In this paper, a highly efficient nucleus-targeted photoacoustic theranostic polymer was developed for fluorescence and photoacoustic dual-mode imaging-guided PA therapy. The prepared polymer consists of nucleus targeting TAT peptide (TAT: YGRKKRRQRRR), hydrophilic chain poly (N,N-dimethylacrylamide) (PDMA), and near-infrared (NIR) light absorbing agent (hCyR), which can self-assemble to form nanoparticles of approximately 28 nm (denoted as TAT-PDMA-hCyR NPs). The designed nanoparticles show excellent nucleus targeting and tumor cell death (up to 80%) caused by DNA damage under pulsed laser irradiation compared to non-nucleus target counterpart PDMA-hCyR NPs without TAT peptide in vitro. As expected, the fluorescence and PA dual-mode imaging observed that TAT-PDMA-hCyR NPs were able to passively target and enrich in tumors, providing an experimental basis for in vivo treatment and thus ensuring a significant tumor inhibition rate (about 92%). In conclusion, this study provides a new and practicable method for the development of nucleus-targeting nanoparticles as potential theranostic agent for in vivo cancer imaging and therapy.

Keywords: photoacoustic therapy, nucleus, near-infrared light, targeted therapy

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Publication history
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Acknowledgements

Publication history

Received: 29 November 2019
Revised: 20 January 2020
Accepted: 22 January 2020
Published: 26 February 2020
Issue date: March 2020

Copyright

© Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature 2020

Acknowledgements

This work was supported by the National Natural Science Foundation of China (No. 81630046) and the Science and Technology Planning Project of Guangdong Province (Nos. 2015B020233016 and 2014B020215003)

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