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Upconversion mesoporous silica nanoparticles co-delivering celecoxib and rose bengal enable multimodal immunogenic and anti-angiogenic therapy for spinal metastasis of non-small cell lung cancer
Oncogene. 2026 Feb 11. doi: 10.1038/s41388-026-03679-y. Online ahead of print.
ABSTRACT
Non-small cell lung cancer (NSCLC) with spinal metastasis represents a clinical challenge due to its aggressive nature, limited treatment options, and profound impact on patient quality of life. Here, we report the development of an innovative upconversion mesoporous silica nanoparticle (UCMS) platform co-loaded with celecoxib and rose bengal (UCMS@CXB/RB), engineered to synergistically combine photodynamic therapy (PDT) and cyclooxygenase-2 (COX-2) inhibition. Upon near-infrared (NIR) irradiation, UCMS@CXB/RB generated abundant reactive oxygen species, triggered immunogenic cell death, and significantly suppressed prostaglandin E2 signaling, leading to reduced angiogenesis and improved antitumor immunity. In vitro and in vivo studies confirmed that this nanoplatform effectively remodeled the tumor microenvironment, inhibited tumor growth, and alleviated cancer-induced spinal dysfunction. Single-cell multi-omics analysis further revealed dynamic crosstalk among immune cells, tumor cells, and endothelial populations, providing mechanistic insights into the multifaceted therapeutic effects of UCMS@CXB/RB. Our results underscore the clinical potential of integrating PDT with targeted COX-2 blockade to address the complex pathophysiology of NSCLC spinal metastasis. This study presents a promising minimally invasive therapeutic strategy with strong translational relevance for managing metastatic NSCLC and improving patient outcomes.
PMID:41673094 | DOI:10.1038/s41388-026-03679-y
Multi-Agent Intelligence for Multidisciplinary Decision-Making in Gastrointestinal Oncology
Integrative spatial analysis reveals tumor heterogeneity and immune colony niche related to clinical outcomes in small cell lung cancer
Cancer Cell. 2025 Feb 14:S1535-6108(25)00030-3. doi: 10.1016/j.ccell.2025.01.012. Online ahead of print.
ABSTRACT
Recent advances have shed light on the molecular heterogeneity of small cell lung cancer (SCLC), yet the spatial organizations and cellular interactions in tumor immune microenvironment remain to be elucidated. Here, we employ co-detection by indexing (CODEX) and multi-omics profiling to delineate the spatial landscape for 165 SCLC patients, generating 267 high-dimensional images encompassing over 9.3 million cells. Integrating CODEX and genomic data reveals a multi-positive tumor cell neighborhood within ASCL1+ (SCLC-A) subtype, characterized by high SLFN11 expression and associated with poor prognosis. We further develop a cell colony detection algorithm (ColonyMap) and reveal a spatially assembled immune niche consisting of antitumoral macrophages, CD8+ T cells and natural killer T cells (MT2) which highly correlates with superior survival and predicts improving immunotherapy response in an independent cohort. This study serves as a valuable resource to study SCLC spatial heterogeneity and offers insights into potential patient stratification and personalized treatments.
PMID:39983726 | DOI:10.1016/j.ccell.2025.01.012
Activation of AMPK ameliorates acute severe pancreatitis by suppressing pancreatic acinar cell necroptosis in obese mice models
Cell Death Discovery, Published online: 30 September 2023; doi:10.1038/s41420-023-01655-z
Activation of AMPK ameliorates acute severe pancreatitis by suppressing pancreatic acinar cell necroptosis in obese mice models