Synergistic therapeutic antitumor effect of PD-1 blockade cellular vesicles in combination with Iguratimod and Rhodium nanoparticles

Abstract

Immune checkpoint blockade has emerged as a significant therapeutic development in immunotherapy during the past decade. However, only a small percentage of cancer patients respond to checkpoint blockade, suggesting that a fundamental knowledge of the underlying processes of immune checkpoint receptor signaling remains elusive and that novel therapeutic medications are needed. Here, the programmed cell death protein 1(PD-1) expressing nanovesicles were developed to enhance T cell activity. Iguratimod (IGU) and Rhodium (Rh) nanoparticles (NPs) were loaded in PD-1 nanovesicles (NVs) for synergistic therapeutic antitumor effects against lung cancer and metastasis. For the first time, this study revealed that IGU exhibits an antitumor effect by inhibiting the phosphorylation of mammalian target of rapamycin (mTOR) and Rh-NPs provided a photothermal effect by improving reactive oxygen species (ROS)-dependent apoptosis in lung cancer cells. IGU-Rh-PD-1 NVs also reduced the migration ability through the epithelial-mesenchymal transition (EMT) pathway. Furthermore, IGU-Rh-PD-1 NVs reached the targeted site and inhibited tumor growth in vivo. This strategy could boost T cell performance and simultaneously possess chemotherapeutic and photothermal therapy to serve as a new combination therapy for lung cancer and potentially other aggressive cancer.