Paeonol-modified Polydopamine Nanoparticles Promote Colitis-associated Cancer Cell Apoptosis via Regulating the IL-6/STAT-3 Signaling Pathway and Downregulating the Expression of Bcl-2

Background: Polydopamine (PDA) shows promising potential in disease diagnosis and targeted drug delivery. Objectives: This study aimed to investigate the role of Paeonol (PAE)-modified PDA nanoparticles (NPs) in the treatment of colitis-associated cancer (CAC). Materials and Methods: First, PAE-modified PDA NPs were prepared, and then the mouse model of the CAC model was set up. The mice were divided into a blank control group, a CAC model group, a PAE group, and PAE + nano group (n = 10). After treatment, cell apoptosis was detected by flow cytometry, and staining was conducted to observe tissues. Additionally, to explore the interaction between signal transducer and activator of transcription 3 (STAT-3) and the effect of PAE-modified PDA NPs, the WP1066 (STAT-3 inhibitor) group and PAE + nano + WP1066 group were established. Results: PAE alleviated the pathological injury of colonic tissue in CAC mice and promoted the apoptosis of CAC cells, and a PDA NPs carrying PAE exhibited a greater curative effect when dramatically decreasing IL-6 and STAT-3 expression. The presence of STAT-3 inhibitors decreased the CAC cell proliferation and induced apoptosis. A combination of PAE + nano and WP1066 resulted in the most significant difference. Conclusion: PAE-modified PDA NPs can attenuate injuries of the colon tissue in CAC mice and promote the apoptosis of CAC cells by inhibiting the IL-6/STAT-3 pathway and increasing the expression level of Bcl-2, thereby improving the condition of CAC.