Lanthanum Carbonate Nanosheets Based Colloidal Hydrogel for Modulating Innate & Adaptive Tumor Immunotherapy by Augmented Cellular Pyroptosis
- 1School of Medicine and Health Zhengzhou Advanced Research Institute of Harbin Institute of Technology Zhengzhou China
- 2School of Food and Biological Engineering Hefei University of Technology Hefei China
- 3School of Biomedical Engineering Anhui Medical University Hefei China
Abstract
Cellular pyroptosis, a pro‐inflammatory form of programmed cell death, emerges as a promising strategy for cancer immunotherapy. However, gene methylation hampers the expression of gasdermin E (GSDME), a pivotal protein in the caspase‐3‐mediated pyroptosis pathway, across numerous malignancies, including triple‐negative breast cancer (TNBC). This study elucidated that a colloidal hydrogel (GDLC hydrogel) loaded with decitabine (DAC) and crosslinked with lanthanum carbonate nanosheets (LCNSs) and gelatin nanoparticles (Gela NPs) could instigate pyroptosis in TNBC cells, specifically 4T1 cells. Within the tumor microenvironment (TME), the synergistic interaction between DAC and La3+ reversed the epigenetic silencing of the GSDME gene, while concurrently activating caspase‐3, thus facilitating pyroptosis induction. Although monotherapy with La3+‐induced apoptosis proved insufficient in tumor suppression, the concurrent inhibition of methyltransferase via DAC markedly suppressed both primary and recurrent tumors. Moreover, the combinatory application of the GDLC hydrogel and immune checkpoint inhibitors effectively neutralized the immunosuppressive TME of TNBC, triggered an anti‐tumor immune response and engendered a sustained immune memory effect. This strategy significantly curtailed tumor recurrence and metastasis, consequently improving the survival rates of mice in the 4T1 tumor‐bearing mouse model. In conclusion, this colloidal hydrogel platform introduced an innovative paradigm for the immunotherapy of triple‐negative breast cancer.
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BibTeX
@article{hong2026lanthanum,
title = {{Lanthanum Carbonate Nanosheets Based Colloidal Hydrogel for Modulating Innate & Adaptive Tumor Immunotherapy by Augmented Cellular Pyroptosis}},
author = {Yang Hong and Haitao Wu and Weitao Wang and Xuan Zhang and Qian Chen and Yaoyu Hu and Zhengbao Zha},
journal = {Advanced Science},
year = {2026},
month = aug,
doi = {10.1002/advs.76966},
url = {https://doi.org/10.1002/advs.76966},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Lanthanum Carbonate Nanosheets Based Colloidal Hydrogel for Modulating Innate & Adaptive Tumor Immunotherapy by Augmented Cellular Pyroptosis
AU - Yang Hong
AU - Haitao Wu
AU - Weitao Wang
AU - Xuan Zhang
AU - Qian Chen
AU - Yaoyu Hu
AU - Zhengbao Zha
PY - 2026
DA - 2026/08/03
JO - Advanced Science
DO - 10.1002/advs.76966
UR - https://doi.org/10.1002/advs.76966
AB - Cellular pyroptosis, a pro‐inflammatory form of programmed cell death, emerges as a promising strategy for cancer immunotherapy. However, gene methylation hampers the expression of gasdermin E (GSDME), a pivotal protein in the caspase‐3‐mediated pyroptosis pathway, across numerous malignancies, including triple‐negative breast cancer (TNBC). This study elucidated that a colloidal hydrogel (GDLC hydrogel) loaded with decitabine (DAC) and crosslinked with lanthanum carbonate nanosheets (LCNSs) and gelatin nanoparticles (Gela NPs) could instigate pyroptosis in TNBC cells, specifically 4T1 cells. Within the tumor microenvironment (TME), the synergistic interaction between DAC and La3+ reversed the epigenetic silencing of the GSDME gene, while concurrently activating caspase‐3, thus facilitating pyroptosis induction. Although monotherapy with La3+‐induced apoptosis proved insufficient in tumor suppression, the concurrent inhibition of methyltransferase via DAC markedly suppressed both primary and recurrent tumors. Moreover, the combinatory application of the GDLC hydrogel and immune checkpoint inhibitors effectively neutralized the immunosuppressive TME of TNBC, triggered an anti‐tumor immune response and engendered a sustained immune memory effect. This strategy significantly curtailed tumor recurrence and metastasis, consequently improving the survival rates of mice in the 4T1 tumor‐bearing mouse model. In conclusion, this colloidal hydrogel platform introduced an innovative paradigm for the immunotherapy of triple‐negative breast cancer.
SN - 2198-3844
ER -