Bufalin CaCO3 nanoparticles triggered pyroptosis through calcium overload via Na+/Ca2+ exchanger reverse for cancer immunotherapy

Bufalin is a promising active ingredient in traditional Chinese medicine but has shown limited anticancer applications due to its toxicity. Here, we report BCNPs@gel, a bufalin-containing CaCO3 nanoparticle hydrogel, for enhancing cancer treatment through inducing cellular pyroptosis. Under the tumo...

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Main Authors: Li, Tingxuan, Zhang, Yitong, Li, Hanyue, Zhang, Hanjie, Xie, Juntao, Li, Zimu, Zhang, Kai, Yu, Yongkang, Mei, Lin
Other Authors: School of Chemistry, Chemical Engineering and Biotechnology
Format: Journal Article
Language:English
Published: 2025
Subjects:
Online Access:https://hdl.handle.net/10356/182783
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author Li, Tingxuan
Zhang, Yitong
Li, Hanyue
Zhang, Hanjie
Xie, Juntao
Li, Zimu
Zhang, Kai
Yu, Yongkang
Mei, Lin
author2 School of Chemistry, Chemical Engineering and Biotechnology
author_facet School of Chemistry, Chemical Engineering and Biotechnology
Li, Tingxuan
Zhang, Yitong
Li, Hanyue
Zhang, Hanjie
Xie, Juntao
Li, Zimu
Zhang, Kai
Yu, Yongkang
Mei, Lin
author_sort Li, Tingxuan
collection NTU
description Bufalin is a promising active ingredient in traditional Chinese medicine but has shown limited anticancer applications due to its toxicity. Here, we report BCNPs@gel, a bufalin-containing CaCO3 nanoparticle hydrogel, for enhancing cancer treatment through inducing cellular pyroptosis. Under the tumor microenvironment's low pH conditions, bufalin and Ca2+ are released from the delivery system. Bufalin serves as a direct anticancer drug and a Na+/K+-ATPase inhibitor by forcing the Na+/Ca2+ exchanger to reverse its function, which transfers Ca2+ into cytoplasm and ultimately causes Ca2+ overload-triggered pyroptosis. Meanwhile, we found that bufalin can upregulate PD-L1 in tumor cells. In combination with the PD-1 antibody, the delivery system showed a greater performance during the cancer treatment. BCNPs@gel enhances antitumor efficiency, reduces systemic side effects, extends antitumor mechanism of bufalin, and provides new strategies for inducing pyroptosis and calcium overload in cancer immunotherapy via Na+/K+-ATPase inhibitor. This work provides an application model for numerous other traditional Chinese medicine ingredients.
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spelling ntu-10356/1827832025-02-25T05:42:59Z Bufalin CaCO3 nanoparticles triggered pyroptosis through calcium overload via Na+/Ca2+ exchanger reverse for cancer immunotherapy Li, Tingxuan Zhang, Yitong Li, Hanyue Zhang, Hanjie Xie, Juntao Li, Zimu Zhang, Kai Yu, Yongkang Mei, Lin School of Chemistry, Chemical Engineering and Biotechnology Medicine, Health and Life Sciences Pyroptosis Bufalin Bufalin is a promising active ingredient in traditional Chinese medicine but has shown limited anticancer applications due to its toxicity. Here, we report BCNPs@gel, a bufalin-containing CaCO3 nanoparticle hydrogel, for enhancing cancer treatment through inducing cellular pyroptosis. Under the tumor microenvironment's low pH conditions, bufalin and Ca2+ are released from the delivery system. Bufalin serves as a direct anticancer drug and a Na+/K+-ATPase inhibitor by forcing the Na+/Ca2+ exchanger to reverse its function, which transfers Ca2+ into cytoplasm and ultimately causes Ca2+ overload-triggered pyroptosis. Meanwhile, we found that bufalin can upregulate PD-L1 in tumor cells. In combination with the PD-1 antibody, the delivery system showed a greater performance during the cancer treatment. BCNPs@gel enhances antitumor efficiency, reduces systemic side effects, extends antitumor mechanism of bufalin, and provides new strategies for inducing pyroptosis and calcium overload in cancer immunotherapy via Na+/K+-ATPase inhibitor. This work provides an application model for numerous other traditional Chinese medicine ingredients. The authors gratefully acknowledge the support of this research by the grants from National Natural Science Foundation of China (82272154), Tianjin Science Fund for Distinguished Young Scholars (22JCJQJC00120), Science and Technology Program of Tianjin City (the Basic Research Cooperation Special Foundation of Beijing-Tianjin-Hebei Region, 22JCZXJC00060), the Fundamental Research Funds for the Central Universities (2021-RC310-005), the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (2021-I2M-1-058 and 2022-I2M-2-003). 2025-02-25T05:42:59Z 2025-02-25T05:42:59Z 2024 Journal Article Li, T., Zhang, Y., Li, H., Zhang, H., Xie, J., Li, Z., Zhang, K., Yu, Y. & Mei, L. (2024). Bufalin CaCO3 nanoparticles triggered pyroptosis through calcium overload via Na+/Ca2+ exchanger reverse for cancer immunotherapy. Nano Letters, 24(40), 12691-12700. https://dx.doi.org/10.1021/acs.nanolett.4c04061 1530-6984 https://hdl.handle.net/10356/182783 10.1021/acs.nanolett.4c04061 39347619 2-s2.0-85206018383 40 24 12691 12700 en Nano Letters © 2024 American Chemical Society. All rights reserved.
spellingShingle Medicine, Health and Life Sciences
Pyroptosis
Bufalin
Li, Tingxuan
Zhang, Yitong
Li, Hanyue
Zhang, Hanjie
Xie, Juntao
Li, Zimu
Zhang, Kai
Yu, Yongkang
Mei, Lin
Bufalin CaCO3 nanoparticles triggered pyroptosis through calcium overload via Na+/Ca2+ exchanger reverse for cancer immunotherapy
title Bufalin CaCO3 nanoparticles triggered pyroptosis through calcium overload via Na+/Ca2+ exchanger reverse for cancer immunotherapy
title_full Bufalin CaCO3 nanoparticles triggered pyroptosis through calcium overload via Na+/Ca2+ exchanger reverse for cancer immunotherapy
title_fullStr Bufalin CaCO3 nanoparticles triggered pyroptosis through calcium overload via Na+/Ca2+ exchanger reverse for cancer immunotherapy
title_full_unstemmed Bufalin CaCO3 nanoparticles triggered pyroptosis through calcium overload via Na+/Ca2+ exchanger reverse for cancer immunotherapy
title_short Bufalin CaCO3 nanoparticles triggered pyroptosis through calcium overload via Na+/Ca2+ exchanger reverse for cancer immunotherapy
title_sort bufalin caco3 nanoparticles triggered pyroptosis through calcium overload via na ca2 exchanger reverse for cancer immunotherapy
topic Medicine, Health and Life Sciences
Pyroptosis
Bufalin
url https://hdl.handle.net/10356/182783
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