Theranostic nanoplatform for high‐performance dual‐modal magnetic resonance imaging‐guided therapy of orthotopic hepatocellular carcinoma

Abstract Magnetic resonance imaging (MRI) techniques are essential for the diagnosis of hepatocellular carcinoma (HCC) and the development of precise treatment strategies. Multifunctional diagnostic agents integrating MRI capabilities have attracted considerable interest in precision oncology. In this study, a biomimetic nanoparticle (HAMM NPs) is engineered through the synthesis of Mn 2+ ‐doped mesoporous polydopamine (Mn‐MPDA) as a drug carrier, followed by loading the hydrophilic sonosensitizer artesunate (ART) and coating with Hepa1‐6 cell membranes. The resulting Hepa1‐6@ART@Mn‐MPDA nanoparticles (HAMM NPs) exhibit enhanced tumor accumulation owing to the homologous targeting capability conferred by the Hepa1‐6 cell membrane. Under the acidic conditions of the tumor microenvironment, HAMM NPs undergo pH‐triggered release of Mn 2+ and ART. HAMM NPs exhibit excellent T 1 /T 2 dual‐modality MRI capability enabling precise liver cancer imaging and MRI‐guided sonodynamic therapy (SDT). Upon ultrasound activation, ART generates cytotoxic reactive oxygen species in an oxygen‐independent manner, which synergizes with Mn 2+ ‐mediated chemodynamic therapy via Fenton‐like reactions. In both subcutaneous and orthotopic HCC models, HAMM NPs effectively inhibit tumor growth. This strategy overcomes the limitations of conventional SDT in hypoxic tumors, offering a promising approach for imaging‐guided combination therapy against deep‐seated tumors.