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Photothermal therapy of tuberculosis using targeting pre-activated macrophage membrane-coated nanoparticles

Nature Nanotechnology (2024)Cite this article

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Abstract

Conventional antibiotics used for treating tuberculosis (TB) suffer from drug resistance and multiple complications. Here we propose a lesion–pathogen dual-targeting strategy for the management of TB by coating Mycobacterium-stimulated macrophage membranes onto polymeric cores encapsulated with an aggregation-induced emission photothermal agent that is excitable with a 1,064 nm laser. The coated nanoparticles carry specific receptors for Mycobacterium tuberculosis, which enables them to target tuberculous granulomas and internal M. tuberculosis simultaneously. In a mouse model of TB, intravenously injected nanoparticles image individual granulomas in situ in the lungs via signal emission in the near-infrared region IIb, with an imaging resolution much higher than that of clinical computed tomography. With 1,064 nm laser irradiation from outside the thoracic cavity, the photothermal effect generated by these nanoparticles eradicates the targeted M. tuberculosis and alleviates pathological damage and excessive inflammation in the lungs, resulting in a better therapeutic efficacy compared with a combination of first-line antibiotics. This precise photothermal modality that uses dual-targeted imaging in the near-infrared region IIb demonstrates a theranostic strategy for TB management.

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Fig. 1: A precise theranostic strategy for TB based on Mycobacterium pre-activated macrophage membrane-coated photothermal nanoparticles.
Fig. 2: Transcriptomic analysis and characterization of M. marinum-stimulated macrophages.
Fig. 3: Characterization of TPE-BT-BBTD and BBTD@PM NPs.
Fig. 4: In vitro targeting and antibacterial activity of BBTD@PM NPs against M. tuberculosis.
Fig. 5: Targeted NIR-IIb imaging of tuberculous granulomas and internal M. tuberculosis with BBTD@PM NPs.
Fig. 6: Antibacterial and anti-inflammatory effects of BBTD@PM NPs in mice with H37Ra-induced pulmonary TB.

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Data availability

The main data that support the findings of this study are available within the Article and its Supplementary Information. There are no data from third-party or publicly available datasets. The transcriptome raw data used in this paper were deposited in the NCBI Sequence Read Archive under accession number PRJNA1031148. Source data are provided with this paper. Other datasets generated during and/or analysed during the current study are available from the corresponding author upon reasonable request.

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Acknowledgements

This research was funded by the National Key Research and Development Program of China (2021YFC2302200, Y.L.), the National Natural Science Foundation of China (82322042, 82272248 and 81972019, Y.L.; 82102360, Y.W.), the China Postdoctoral Science Foundation (2022M720730, B.L.), the Natural Science Foundation of Guangdong Province for Distinguished Young Scholars (2022B1515020089, Y.L.), the Basic and Applied Basic Research Foundation of Guangdong Province (2021A1515110209 and 2022A1515140080, B.L.; 2020A1515110529, Y.W.), the Comprehensive Research Project of the National Natural Science Foundation of China (82241059, J. Zheng), the Zhongnanshan Medical Foundation of Guangdong Province (ZNSA-2021012, Y.L.) and the Training project of the National Science Foundation for Outstanding/Distinguished Young Scholars of Southern Medical University (C620PF0217, Y.L.).

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Author notes

  1. These authors contributed equally: Bin Li, Wei Wang, Lu Zhao, Yunxia Wu.

Authors and Affiliations

  1. Molecular Diagnosis and Treatment Center for Infectious Diseases, Dermatology Hospital of Southern Medical University, Guangzhou, China

    Bin Li, Wei Wang, Xiaoxue Li, Yi Feng, Judun Zheng, Bowen Shu, Jiamei Wang, Huanhuan Wang, Lingjie He & Yuhui Liao

  2. School of Inspection, Ningxia Medical University, Yinchuan, China

    Bin Li & Yuhui Liao

  3. Institute of Translational Medicine, Department of Clinical Laboratory & Department of Burn Surgery, The First People’s Hospital of Foshan, Foshan, China

    Bin Li, Lu Zhao, Yunxia Wu & Qiuxia Gao

  4. Center for AIE Research, Shenzhen Key Laboratory of Polymer Science and Technology, Guangdong Research Center for Interfacial Engineering of Functional Materials, College of Materials Science and Engineering, Shenzhen University, Shenzhen, China

    Dingyuan Yan, Dong Wang & Ben Zhong Tang

  5. Department of Critical Care Medicine, Department of Emergency, Renmin Hospital of Wuhan University, Wuhan, China

    Yan Yan, Yunlong Zhang & Mingliang Pan

  6. Engineering Research Center of Tibetan Medicine Detection Technology, Ministry of Education, Xizang Minzu University, Xianyang, China

    Jie Zhang

  7. School of Science and Engineering, Shenzhen Institute of Aggregate Science and Technology, The Chinese University of Hong Kong, Shenzhen, China

    Ben Zhong Tang

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Contributions

B.L., W.W., L.Z., Y.W. and Y.L. designed the research. B.L., W.W., L.Z., Y.W., X.L., D.Y., Q.G., Y.Y., J. Zhang, Y.F., J. Zheng, B.S., J.W. and H.W. performed the research. D.W. and B.Z.T. provided professional support for animal studies. All authors analysed and interpreted the data. B.L., W.W., L.Z. and Y.W. wrote the paper.

Corresponding authors

Correspondence to Dong Wang, Ben Zhong Tang or Yuhui Liao.

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Supplementary information

Supplementary Information

Supplementary Figs. 1–37, Table 1 and Discussions.

Reporting Summary

Supplementary Video 1

Time-dependent NIR-IIb imaging of a mouse with TB in a supine position after intravenous injection of BBTD@PM NPs.

Supplementary Data 1

Statistical source data for Supplementary Figs. 1, 2, 7, 12–14, 16–20, 22, 24 and 32–35.

Supplementary Data 2

ChemDraw file for the synthetic route to TPE-BT-BBTD.

Source data

Source Data Fig. 2

Unprocessed western blots.

Source Data Fig. 2

Statistical source data.

Source Data Fig. 3

Unprocessed western blots.

Source Data Fig. 3

Statistical source data.

Source Data Fig. 4

Statistical source data.

Source Data Fig. 5

Statistical source data.

Source Data Fig. 6

Statistical source data.

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Li, B., Wang, W., Zhao, L. et al. Photothermal therapy of tuberculosis using targeting pre-activated macrophage membrane-coated nanoparticles. Nat. Nanotechnol. (2024). https://doi.org/10.1038/s41565-024-01618-0

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