Macrophage reprogramming combined with enhanced photodynamic therapy increases the patency of malignant esophageal obstruction after stenting.
Haoyang XuYiran ZhangSheng GuoHui FangLiming WeiGuangchen HeYingsheng ChengYueqi ZhuPublished in: Nanoscale (2024)
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 2 @MnO 2 nanoparticles was designed, for which a dense δ-MnO 2 coating was synthesized using a novel one-step REDOX reaction. This stent reverses the hypoxic tumor microenvironment (TME) via explosive oxygen generation, thereby increasing the efficacy of photodynamic therapy (PDT). Furthermore, Mn 2+ reprograms the polarity of tumor associated macrophages (TAMs) in the immunosuppressed TME to effectively activate innate anti-tumor immunity in combination with PDT. Mn 2+ 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 2 @MnO 2 effectively suppresses the apoptosis of TAMs to enhance their anti-tumor effect. The proposed strategy highlights the multifaceted role of Ce6-SiO 2 @MnO 2 in the treatment of advanced esophageal cancer.
Keyphrases
- photodynamic therapy
- fluorescence imaging
- binding protein
- immune response
- transcription factor
- energy transfer
- multiple sclerosis
- magnetic nanoparticles
- oxidative stress
- drug delivery
- endoplasmic reticulum stress
- adipose tissue
- cell proliferation
- cell death
- nuclear factor
- cell cycle arrest
- metal organic framework
- protein protein
- long non coding rna
- transition metal
- toll like receptor
- electron transfer