Pathology-Driven Design of a Biomimetic Ferromagnetic Nanomedicine for Dual-Mode Treatment of Ulcerative Colitis and Colitis-Associated Colorectal Cancer

Abstract

The pathological features of ulcerative colitis (UC) involve systemic abnormalities, including immune dysregulation, iron deficiency, and microbiota imbalance, and these alterations contribute to an increased risk of colitis-associated colorectal cancer (CAC). Current therapeutic strategies remain insufficient to address these pathological features and restore physiological homeostasis. Here, a dual-duty nanomedicine (MAC@EGCG-Fe3O4), engineered with an inflammation-homing M2-type macrophage membrane “shell” is rationally designed and developed, which encapsulates silk fibroin nanocages loading with epigallocatechin gallate (EGCG) and ferromagnetic nanoparticles (Fe3O4). Upon intraperitoneal injection and exposure to an alternating magnetic field (AMF), the nanomedicine selectively accumulated in inflamed lesions, enabling site-specific therapeutic effects. Controlled AMF irradiation provided localized mild hyperthermia and reductive EGCG for UC treatment or hyperpyrexia and oxidative EGCG for treating CAC. Moreover, this therapeutic strategy reprogrammed colonic immune responses, restored mucosal integrity, alleviated iron deficiency, and modulated microbiota and its metabolites. The study highlights the therapeutic potential of a single pathology-driven nanomedicine against both UC and CAC through AMF manipulation.