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Nano Research 2023, 16(5): 7148-7163 https://doi.org/10.1007/s12274-022-5313-3
Research Article | Issue | Published: 23 December 2022

A novel two-dimensional nanoheterojunction via facilitating electron–hole pairs separation for synergistic tumor phototherapy and immunotherapy

Show Author's Information Xiaoge Zhang§,  Xiaomei Chen§,  Peng Zhang,  Meiting Li,  Miao Feng,  Yaqian Zhang,  Lili Cheng,  Junjie Tang,  Langtao Xu,  Yadong Liu,  Zhuoyin Liu,  Zhong Cao( ),  Jie Liu( )
School of Biomedical Engineering, Shenzhen Campus of Sun Yat-sen University, Shenzhen 518107, China

§ Xiaoge Zhang and Xiaomei Chen contributed equally to this work.

Keywords:
immunotherapy, photodynamic therapy, photothermal therapy, mitochondrial targeting, two-dimensional nanoheterojunction
Topics:
Biomaterials
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Zhang X, Chen X, Zhang P, et al. A novel two-dimensional nanoheterojunction via facilitating electron–hole pairs separation for synergistic tumor phototherapy and immunotherapy. Nano Research, 2023, 16(5): 7148-7163. https://doi.org/10.1007/s12274-022-5313-3
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Abstract Full text Electronic supplementary material About this article

Nanomaterial-mediated phototherapy in tumor treatment has been developed rapidly in the past few years due to its noninvasive character. However, the low energy conversion efficiency and high recombination rate of the photo-triggered electron–hole pairs of single nano-agent limit the phototherapy efficiency. Herein, we constructed a novel two-dimensional nanoheterojunction MoS2-Ti3C2 (MT), which allowed a high photothermal conversion efficiency (59.1%) as well as an effective separation of photo-triggered electron–hole pairs for reactive oxygen species (ROS) generation under single 808 nm laser irradiation. Upon the modification of the mitochondrial targeted molecule (3-proxycarboxylic) triphenyl phosphine bromide (TPP) and 4T1 cell membrane, m@MoS2-Ti3C2/TPP (m@MTT) could effectively target to the tumor cell and further locate to the mitochondria to amplify tumor-specific oxidative stress, which not merely effectively inhibits the local tumor growth but also induces tumor immunogenic cell death (ICD) for activating antitumor immune response. Additionally, cytosine guanine dinucleotide (CPG), as a Toll-like receptor 9 (TLR9) agonist, was further introduced to the system to boost adaptive immune responses, resulting in improved level of cytotoxic T cells as well as a decrease in the number of regulatory T cells. In vivo antitumor mechanism studies demonstrated that not only the primary and distant tumors in 4T1 bearing-tumor mice model were significantly inhibited, but also the lung metastasis of tumor was effectively suppressed. Therefore, this work revealed the ROS generation mechanism of MT nanoheterojunction and provided a novel strategy to fabricate a biomedically applicable MT nanoheterojunction for tumor treatment.


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Abstract
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Electronic supplementary material
About this article

A novel two-dimensional nanoheterojunction via facilitating electron–hole pairs separation for synergistic tumor phototherapy and immunotherapy

Show Author's information Xiaoge Zhang§, Xiaomei Chen§, Peng Zhang, Meiting Li, Miao Feng, Yaqian Zhang, Lili Cheng, Junjie Tang, Langtao Xu, Yadong Liu, Zhuoyin Liu, Zhong Cao( ), Jie Liu( )
School of Biomedical Engineering, Shenzhen Campus of Sun Yat-sen University, Shenzhen 518107, China

§ Xiaoge Zhang and Xiaomei Chen contributed equally to this work.

Abstract

Nanomaterial-mediated phototherapy in tumor treatment has been developed rapidly in the past few years due to its noninvasive character. However, the low energy conversion efficiency and high recombination rate of the photo-triggered electron–hole pairs of single nano-agent limit the phototherapy efficiency. Herein, we constructed a novel two-dimensional nanoheterojunction MoS2-Ti3C2 (MT), which allowed a high photothermal conversion efficiency (59.1%) as well as an effective separation of photo-triggered electron–hole pairs for reactive oxygen species (ROS) generation under single 808 nm laser irradiation. Upon the modification of the mitochondrial targeted molecule (3-proxycarboxylic) triphenyl phosphine bromide (TPP) and 4T1 cell membrane, m@MoS2-Ti3C2/TPP (m@MTT) could effectively target to the tumor cell and further locate to the mitochondria to amplify tumor-specific oxidative stress, which not merely effectively inhibits the local tumor growth but also induces tumor immunogenic cell death (ICD) for activating antitumor immune response. Additionally, cytosine guanine dinucleotide (CPG), as a Toll-like receptor 9 (TLR9) agonist, was further introduced to the system to boost adaptive immune responses, resulting in improved level of cytotoxic T cells as well as a decrease in the number of regulatory T cells. In vivo antitumor mechanism studies demonstrated that not only the primary and distant tumors in 4T1 bearing-tumor mice model were significantly inhibited, but also the lung metastasis of tumor was effectively suppressed. Therefore, this work revealed the ROS generation mechanism of MT nanoheterojunction and provided a novel strategy to fabricate a biomedically applicable MT nanoheterojunction for tumor treatment.

Keywords: immunotherapy, photodynamic therapy, photothermal therapy, mitochondrial targeting, two-dimensional nanoheterojunction

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Publication history
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Acknowledgements

Publication history

Received: 03 September 2022
Revised: 08 November 2022
Accepted: 10 November 2022
Published: 23 December 2022
Issue date: May 2023

Copyright

© Tsinghua University Press 2022

Acknowledgements

This work was supported by the National Natural Science Foundation of China (No. 51773231), Shenzhen Science and Technology Project (No. JCYJ20190807160801664), and the Foundation of Guangdong Provincial Key Laboratory of Sensor Technology and Biomedical Instrument (No. 2020B1212060077).

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