Enhanced cancer immunotherapy through synergistic ferroptosis and immune checkpoint blockade using cell membrane-coated nanoparticles
Yeteng Mu, Yuxin Fan, Lianping He, Nannan Hu, Xue Han, Xingang Guan, Zhijian Zheng
Abstract
Abstract Background Immune checkpoint blockade (ICB) has achieved unprecedented success in inhibiting the progression and metastasis of many cancers. However, ICB regents as a single treatment have a relatively low overall response rate due to the tumor’s low immunogenicity and immunosuppressive microenvironment. Herein, we report a PD-1 cellular membrane-coated ferroptosis nanoinducer to potentiate cancer immunotherapy toward triple-negative breast cancer. Results This study demonstrates that PD-1 membrane-coated RSL3 nanoparticles (PD-1@RSL3 NPs) have the ability to disrupt the PD-1/PD-L1 axis, leading to the activation of antitumor immunity in breast cancer. In addition, the nanoparticles promote the induction of tumor cell ferroptosis through GPX4 inhibition, enhanced infiltration of CD8 + T cells, and maturation of dendritic cells. The potentiated antitumor immune response induced by PD-1@RSL3 NPs significantly delayed tumor progression and extended the survival rate of mice with breast cancer xenografts. Conclusions Our study suggest the potential of PD-1@RSL3 NPs as an effective therapeutic approach for breast cancer by promoting tumor cell ferroptosis and inducing antitumor immunity.