To enhance the comprehensive treatment effect of triple-negative breast cancer, a pH-responsive core-shell manganese phosphate nano-regulator was prepared to reprogram the tumor microenvironment bi-directionally. (1) “Brakes off”: Using siPD-L1 to inhibit PD-L1 expression to restore CD8+ T cell function. 2) “Step on the accelerator”: Based on Mn2+’s effect, promoting CD8+ T cell infiltration and maturation.
Abstract:
The insufficient infiltration and functional inhibition of CD8+ T cells due to tumor microenvironment (TME) are considered enormous obstacles to anti-tumor immunotherapy. Herein, a pH-responsive core-shell manganese phosphate nanomodulator co-loading siPD-L1 and Mn2+ into nanoparticles coated with hyaluronic acid was prepared, which was aimed at the bidirectional reprogramming the tumor microenvironment: (1) “Brakes off,” restoring CD8+ T cells function by siPD-L1 knockdowning PD-L1 expression of tumor cells; (2) “Step on the accelerator,” promoting CD8+ T cells infiltration in tumors tissue based on the multidimensional immune effects of Mn2+ (immunogenic cell death induced the enhancing cGAS-STING pathway, the proliferation and maturation of relative immune cells). Additionally, this strategy could induce macrophage polarization and inhibit the regulatory T cells in tumor site. This work provided a manganese phosphate nanomodulator to reprogram the immune TME for an enhanced comprehensive anti-tumor effect of triple negative breast cancer, which offers a robust method for tumor immunotherapy in future clinical applications.
Author list:
Fei Xia†, Yuqian Lu†, Zipeng Gong†, Qingchao Tu†, Shuntao Liang, Chen Wang, HaiLu Yao, LinYing Zhong, Yuanfeng Fu, Pengbo Guo, Yichong Hou, Xinyu Zhou, Li Zou, Licheng Gan, Weiqi Chen, Jiawei Yan, Junzhe Zhang, Huanhuan Pang, Yuqing Meng, Qiaoli Shi, Chen Pan, Xiaomei Tao*, Jigang Wang*, Qingfeng Du*, Chong Qiu*
How to cite:
F. Xia, Y. Lu, Z. Gong, Q. Tu, S. Liang, C. Wang, H. Yao, L. Zhong, Y. Fu, P. Guo, Y. Hou, X. Zhou, L. Zou, L. Gan, W. Chen, J. Yan, J. Zhang, H. Pang, Y. Meng, Q. Shi, C. Pan, X. Tao, J. Wang, Q. Du, C. Qiu, Exploration 2025, 70009.
https://doi.org/10.1002/EXP.70009