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Effective therapeutic strategies to precisely eradicate primary tumors with minimal side effects on normal tissue, inhibit metastases, and prevent tumor relapses, are the ultimate goals in the battle against cancer. We report a novel therapeutic strategy that combines adjuvant black phosphorus nanoparticle-based photoacoustic (PA) therapy with checkpoint-blockade immunotherapy. With the mitochondria targeting nanoparticle, PA therapy can achieve localized mechanical damage of mitochondria via PA cavitation and thus achieve precise eradication of the primary tumor. More importantly, PA therapy can generate tumor-associated antigens via the presence of the R848-containing nanoparticles as an adjuvant to promote strong antitumor immune responses. When combined with the checkpoint-blockade using anti-cytotoxic T-lymphocyte antigen-4, the generated immunological responses will further promote the infiltrating CD8 and CD4 T-cells to increase the CD8/Foxp3 T-cell ratio to inhibit the growth of distant tumors beyond the direct impact range of the PA therapy. Furthermore, the number of memory T cells detected in the spleen is increased, and these cells inhibit tumor recurrence. This proposed strategy offers precise eradication of the primary tumor and can induce long-term tumor-specific immunity.

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Publication history

Received: 23 June 2020
Revised: 28 July 2020
Accepted: 01 August 2020
Published: 29 August 2020
Issue date: December 2020

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

Acknowledgements

This research was supported by the National Natural Science Foundation of China (Nos. 11604105 and 81630046); the Science and Technology Planning Project of Guangdong Province, China (Nos. 2015B020233016, 2014B020215003, and 2014B050504009); the Scientific and Technological Planning Project of Guangzhou City (Nos. 201805010002 and 201804010360), and the Science and Technology Program of Guangzhou (No. 2019050001)

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Reprints and Permission requests may be sought directly from editorial office.
Email: nanores@tup.tsinghua.edu.cn

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