Hollow Mesoporous Manganese Dioxide Nanoprobes for Hepatocellular Carcinoma Diagnosis and Therapy

Chemotherapy remains a standard treatment for hepatocellular carcinoma (HCC). Nevertheless, the complexity of the tumor microenvironment (TME) significantly reduces the efficiency of drug delivery and penetration into tumor tissues. Nanosized probes exhibit unique advantages in passive targeting via the enhanced permeability and retention (EPR) effect, enabling efficient identification, deep-tissue imaging and targeted drug transport for HCC management. In this study, an magnetic resonance-fluorescence bimodal imaging nanoprobe with a well-defined nanoscale structure (≈190 nm hydrodynamic diameter), designated cRGD-MnO2/DOX@PDA-Cy5.5 (cHMDPC), was developed for HCC precision theranostics. This nanostructured platform is responsive to the TME, exhibits specific targeting, enhances contrast in T1-weighted magnetic resonance imaging (MRI), and has photothermal properties that act synergistically with chemotherapy, improving antitumor efficacy. In vitro studies demonstrated that cHMDPC nanoprobes were more effectively internalized by HCC cells, indicating strong targeting specificity. This nanoprobe markedly suppressed cell proliferation and promoted apoptosis. In vivo experiments further confirmed its excellent MRI performance, significant tumor suppression, and high biocompatibility. In summary, the cHMDPC nanoprobe achieves targeted drug delivery, facilitates early diagnosis, and enhances treatment outcomes, providing a novel strategy for HCC theranostics.