Macrophage reprogramming combined with enhanced photodynamic therapy increases the patency of malignant esophageal obstruction after stenting

• Published in: Nanoscale Vol. 16; no. 34; pp. 16035 - 16047
• Main Authors: Xu, Haoyang, Zhang, Yiran, Guo, Sheng, Fang, Hui, Wei, Liming, He, Guangchen, Cheng, Yingsheng, Zhu, Yueqi
• Format: Journal Article
• Language: English
• Published: England Royal Society of Chemistry 29.08.2024
• Subjects: Animals; Anticancer properties; Apoptosis - drug effects; Cancer; Cell Line, Tumor; Chemical synthesis; Chlorophyllides; Esophageal cancer; Esophageal Neoplasms - drug therapy; Esophageal Neoplasms - pathology; Esophageal Neoplasms - therapy; Humans; Macrophages; Macrophages - drug effects; Macrophages - metabolism; Manganese Compounds - chemistry; Manganese Compounds - pharmacology; Manganese dioxide; Mice; Mice, Inbred BALB C; Nanoparticles - chemistry; Occlusion; Oxides - chemistry; Oxides - pharmacology; Photochemotherapy; Photodynamic therapy; Photosensitizing Agents - chemistry; Photosensitizing Agents - pharmacology; Photosensitizing Agents - therapeutic use; Redox reactions; Silicon dioxide; Silicon Dioxide - chemistry; Stents; Surgical implants; Tumor Microenvironment - drug effects
• ISSN: 2040-3364; 2040-3372; 2040-3372
• DOI: 10.1039/d4nr01140f

Esophageal cancer (EC) is a disease characterized by progressive malignant obstruction. Stent implantation restores lumen patency, but tumor progression is likely to cause re-occlusion shortly. An esophageal stent loaded with Ce6-SiO @MnO nanoparticles was designed, for which a dense δ-MnO coating was synthesized using a novel one-step REDOX reaction. This stent reverses the hypoxic tumor microenvironment (TME) explosive oxygen generation, thereby increasing the efficacy of photodynamic therapy (PDT). Furthermore, Mn reprograms the polarity of tumor associated macrophages (TAMs) in the immunosuppressed TME to effectively activate innate anti-tumor immunity in combination with PDT. Mn downregulates the high mobility group box 1 protein (HMGB1), upregulates the signal transducer and activator of transcription 1 (STAT1) mRNA, and ultimately expresses the tumor inhibition effect of TAMs. Additionally, Ce6-SiO @MnO effectively suppresses the apoptosis of TAMs to enhance their anti-tumor effect. The proposed strategy highlights the multifaceted role of Ce6-SiO @MnO in the treatment of advanced esophageal cancer.