Radiotherapy (RT), as one of the main methods in the clinical treatment of various malignant tumors, would induce systemic immunotherapeutic effects by triggering immunogenic cell death (ICD) of cancer cells. However, the antitumor immune responses produced by RT-induced ICD alone usually are not robust enough to eliminate distant tumors and thus ineffective against cancer metastases. Herein, a biomimetic mineralization method for facile synthesis of MnO 2 nanoparticles with high antiprogrammed death ligand 1 (αPDL1) encapsulation efficiency (αPDL1@MnO 2 ) is proposed to reinforce RT-induced systemic antitumor immune responses. This therapeutic nanoplatformsmediated RT can significantly improve the killing of tumor cells and effectively evoke ICD by overcoming hypoxia-induced radioresistance and reprogramming the immunosuppressive tumor microenvironment (TME). Furthermore, the released Mn 2+ ions from αPDL1@MnO 2 under acidic tumor pH can activate the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway and facilitate the dendritic cells (DCs) maturation. Meanwhile, αPDL1 released from αPDL1@MnO 2 nanoparticles would further promote the intratumoral infiltration of cytotoxic T lymphocytes (CTLs) and trigger systemic antitumor responses, resulting in a strong abscopal effect to effectively inhibit tumor metastases. Overall, the biomineralized MnO 2 -based nanoplatforms offer a simple strategy for TME modulation and immune activation, which are promising for enhanced RT immunotherapy.

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Exposure to fine particulate matter with a diameter ≤2.5 μm (PM2.5) can result in serious inflammation and oxidative stress in lung tissue. However, there is presently very few effective treatments for PM2.5-induced many pulmonary diseases, such as acute lung injury (ALI). Herein, curcumin-loaded reactive oxygen species (ROS)-responsive hollow mesoporous silica nanoparticles (Cur@HMSN-BSA) are proposed for scavenging the intracellular ROS and suppressing inflammatory responses against PM2.5-induced ALI. The prepared nanoparticles were coated with bovine serum albumin (BSA) via an ROS-sensitive thioketal (TK)-containing linker, in which the TK-containing linker would be cleaved by the excessive amounts of ROS in inflammatory sites to induce the detachment of BSA from the nanoparticles surface and thus triggering release of loaded curcumin. The Cur@HMSN-BSA nanoparticles could be used as ROS scavengers because of their excellent ROS-responsiveness, which were able to efficiently consume high concentrations of intracellular ROS. Furthermore, it was also found that Cur@HMSN-BSA downregulated the secretion of several important pro-inflammatory cytokines and promoted the polarization from M1 phenotypic macrophages to M2 phenotypic macrophages for eliminating PM2.5-induced inflammatory activation. Therefore, this work provided a promising strategy to synergistically scavenge intracellular ROS and suppress the inflammation responses, which may serve as an ideal therapeutic platform for pneumonia treatment.