251. Bufalin CaCO 3 Nanoparticles Triggered Pyroptosis through Calcium Overload via Na + /Ca 2+ Exchanger Reverse for Cancer Immunotherapy.
- Author
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Li T, Zhang Y, Li H, Zhang H, Xie J, Li Z, Zhang K, Yu Y, and Mei L
- Subjects
- Humans, Animals, Mice, Cell Line, Tumor, Sodium-Calcium Exchanger metabolism, Antineoplastic Agents pharmacology, Antineoplastic Agents chemistry, Antineoplastic Agents therapeutic use, Immunotherapy methods, Tumor Microenvironment drug effects, Neoplasms drug therapy, Neoplasms metabolism, Sodium-Potassium-Exchanging ATPase metabolism, Sodium-Potassium-Exchanging ATPase antagonists & inhibitors, Bufanolides pharmacology, Bufanolides chemistry, Bufanolides therapeutic use, Nanoparticles chemistry, Calcium metabolism, Pyroptosis drug effects, Calcium Carbonate chemistry
- Abstract
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 CaCO
3 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.- Published
- 2024
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