| Reprogramming the Tumor Microenvironment Through Cortisol-Modulating Nanomedicine |
| Paper ID : 1029-ISCH |
| Authors |
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Shima A Aldurini *1, Medhat wahba Shafaa2, Emad Tolba3, Ayman Meselhy4, Bothaina Abd El-Hady5 1Teacher Assistant at the Faculty of Science, Helwan University. Completed a Master’s degree in Biomaterials and is currently pursuing a Ph.D. in Biomaterials at Helwan University, Egypt. 2Helwan 3Prof. Emad Tolba is a senior researcher in the Biomaterials Department, Chemical Industries Division at the National Research Centre (NRC), Cairo, Egypt. He earned his Ph.D. from the Institute for Physiological Chemistry, University Medical Center, Johannes Gutenberg University Mainz, Germany, where he focused on bioactive materials for tissue engineering and regenerative medicine. 4Biophysics instructor 5proffessor of polymer National Research Center, Dokki, Cairo |
| Abstract |
| Abstract Chronic stress and abnormal cortisol signaling establish a self-reinforcing gut–brain loop that contributes to inflammatory bowel disease (IBD) and colorectal cancer (CRC). While acute cortisol suppresses inflammation, persistent elevation disrupts intestinal barrier function, induces microbial dysbiosis, and activates NF-κB through TLR4, driving sustained inflammation and epithelial damage. Breaking this loop represents a promising therapeutic approach. We designed a dual-drug nanomedicine based on chondroitin sulfate–chitosan coated liposomes (CHS/CS hybrid liposomes) for co-delivery of curcumin (CURC), a natural NF-κB inhibitor, and dexamethasone (DEXA), a glucocorticoid anti-inflammatory agent. The optimized formulation (CHS_D@L_C) achieved nanoscale size (~80–90 nm), confirmed by TEM/SEM, with high encapsulation efficiency and stable morphology. In a DSS-induced colitis rat model, CHS_D@L_C preserved DNA integrity as shown by Feulgen staining and reduced colonic tissue injury compared with untreated colitis. Biochemical analyses demonstrated decreased oxidative stress and inflammatory markers (TNF-α, IL-6, MDA), consistent with synergistic activity: DEXA providing systemic immunosuppression and CURC locally inhibiting NF-κB signaling. This work highlights a novel dual-drug nanocarrier capable of disrupting the cortisol–dysbiosis–NF-κB loop that drives colorectal pathology. The CHS_D@L_C formulation shows potential as a targeted therapy for colitis-associated CRC by combining systemic inflammation control with localized DNA protection. |
| Keywords |
| Cortisol–gut axis; Colorectal cancer; NF-κB; Liposome–chondroitin sulfate; Curcumin; Dexamethasone |
| Status: Abstract Accepted (Poster Presentation) |