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Metformin-Mediated Fast Charge-Reversal Nanohybrid for Deep Penetration Piezocatalysis-Augmented Chemodynamic Immunotherapy of Cancer

Wang, Yuan, Tang, Qingshuang, Wu, Ruiqi, Yang, Shiyuan, Geng, Zhishuai, He, Ping, Li, Xiaoda, Chen, Qingfeng, Liang, Xiaolong·2024·ACS Nano
DOI 10.1021/acsnano.3c11174
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Abstract

Immune checkpoint blockade (ICB) therapy still suffers from insufficient immune response and adverse effect of ICB antibodies. Chemodynamic therapy (CDT) has been demonstrated to be an effective way to synergize with ICB therapy. However, a low generation rate of reactive oxygen species and poor tumor penetration of CDT platforms still decline the immune effects. Herein, a charge-reversal nanohybrid Met@BF containing both Fe 3 O 4 and BaTiO 3 nanoparticles in the core and Metformin (Met) on the surface was fabricated for tumor microenvironment (TME)- and ultrasound (US)-activated piezocatalysis-chemodynamic immunotherapy of cancer. Interestingly, Met@BF had a negative charge in blood circulation, which was rapidly changed into positive when exposed to acidic TME attributed to quaternization of tertiary amine in Met, facilitating deep tumor penetration. Subsequently, with US irradiation, Met@BF produced H 2 O 2 based on piezocatalysis of BaTiO 3 , which greatly enhanced the Fenton reaction of Fe 3 O 4 , thus boosting robust antitumor immune response. Furthermore, PD-L1 expression was inhibited by the local released Met to further augment the antitumor immune effect, achieving effective inhibitions for both primary and metastatic tumors. Such a combination of piezocatalysis-enhanced chemodynamic therapy and Met-mediated deep tumor penetration and downregulation of PD-L1 provides a promising strategy to augment cancer immunotherapy.

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Metadata

Authors
Wang, Y., Tang, Q., Wu, R., Yang, S., Geng, Z., He, P., Li, X., Chen, Q., & Liang, X.
Venue
ACS Nano
Publisher
American Chemical Society (ACS)
Published
2024-02-12
Volume
18
Issue
8
Pages
6314-6332
ISSN
  • 1936-0851
  • 1936-086X
DOI
10.1021/acsnano.3c11174
Cited by
49
References
2
Language
en
Licence
Funders
  • Peking University Third Hospital (BYSYZD2019018, jyzc2018-02, BYSY2015023)
  • Beijing Municipal Natural Science Foundation (JQ22024)
  • National Natural Science Foundation of China (32271443)

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CoChat. (2026). Citation check: Metformin-Mediated Fast Charge-Reversal Nanohybrid for Deep Penetration Piezocatalysis-Augmented Chemodynamic Immunotherapy of Cancer. https://app.cochat.ai/papers/10.1021/acsnano.3c11174
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Wang, Y., Tang, Q., Wu, R., Yang, S., Geng, Z., He, P., Li, X., Chen, Q., & Liang, X. (2024). Metformin-Mediated Fast Charge-Reversal Nanohybrid for Deep Penetration Piezocatalysis-Augmented Chemodynamic Immunotherapy of Cancer. ACS Nano. https://doi.org/10.1021/acsnano.3c11174