Spatiotemporally Controlled Co-Treatment of Lung Cancer and Pulmonary Immune-Related Adverse Events by Inhalable Albumin-Chaperoned Ultrathin MnO 2 Nanosheets

作者：Yanze Yin, Zhimin Chen, Changjie Yang, Han Du, Gening Jiang, Ding‐Kun Ji, Jie Dai · 发表于：ACS Nano · 年份：2025 · DOI：10.1021/acsnano.5c01888 · 被引用次数：12 · 研究领域：Nanoplatforms for cancer theranostics、Advanced Nanomaterials in Catalysis、Neutrophil, Myeloperoxidase and Oxidative Mechanisms

Cancer immunotherapy is often associated with immune-related adverse events (irAE), particularly in the lungs, which can lead to treatment discontinuation and negatively impact patient outcomes. In this study, we explore a spatiotemporally controlled cotreatment of lung cancer and pulmonary irAE using inhalable albumin-chaperoned ultrathin MnO 2 nanosheets (MnO 2 @BSA). The MnO 2 @BSA exhibits efficient reactive oxygen species scavenging and NIR-II photothermal properties. The inhalation route enhances MnO 2 @BSA accumulation in the lungs and tumor tissue, offering localized treatment with reduced systemic toxicity. We demonstrate that ultrathin MnO 2 @BSA nanosheets can inhibit the formation of neutrophil extracellular traps (NETs) by reducing reactive oxygen species (ROS) in neutrophils, thereby alleviating inflammation associated with irAE. In animal models, inhaled MnO 2 @BSA reduced lung injury and inflammatory cell infiltration, while also decreasing pro-inflammatory cytokine levels, such as TNF-α, IL-1β, and IL-6. Simultaneously, MnO 2 @BSA displays strong photothermal properties under 1064 nm laser irradiation, effectively ablating tumors. This photothermal therapy also induces immunogenic cell death (ICD), promoting the reuse of activated CD8+ T cells to enhance antitumor immunity. These dual effects─tumor destruction and irAE mitigation─highlight MnO 2 @BSA’s potential as a therapeutic platform for addressing the challenges of immunotherapy in lung cancer. We antici...