A Study on Overcoming Post‐TACE Drug Resistance in HCC Based on Controllable Oxygen Release‐Magnetic Hyperthermia Therapy

Abstract Drug‐eluting bead transcatheter arterial chemoembolization (D‐TACE) is one of the first‐line treatment for intermediate hepatocellular carcinoma (HCC). However, the dual hypoxia microenvironment, due to inherent tumor hypoxia and TACE‐induced hypoxia, triggers drug resistance in HCC. To address this challenge, the study develops multicavitary microspheres capable of encapsulating oxygen and harnessing magnetic hyperthermia to enhance oxygen permeability. The novel multicavitary oxygen‐encapsulated magnetothermal drug‐eluting microspheres (OTD‐Ms) effectively reduce hypoxia‐related proteins (HIF‐1α, VEGF‐A) and drug resistance (P‐gp) both in vitro and in vivo. Moreover, these microspheres demonstrate improved TACE efficacy and enhance survival rates in a rabbit VX‐2 tumor model, suggesting their potential for HCC treatment.