Therapeutic Potential of Nanoscale Metal–Organic Frameworks in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) represents the predominant type of primary liver cancer and remains a major global health concern. Current therapeutic strategies—such as surgical resection, radiation, and chemotherapy—provide clinical benefits but are frequently accompanied by considerable adverse effects. Consequently, identifying alternative treatment modalities and developing strategies that allow the use of lower drug doses without compromising therapeutic outcomes are essential goals in HCC management. Among emerging nanoscale platforms, metal–organic frameworks (MOFs) have attracted exceptional interest as promising candidates for targeted drug delivery in cancer therapy. Their inherent characteristics, including highly ordered porosity, large surface area, tunable cavities, adjustable chemical functionality, and remarkable drug-loading capacity, set them apart from conventional porous nanomaterials. Owing to their hierarchical architecture, MOFs are especially suitable for multimodal and synergistic anti-cancer treatments. MOF-based systems have demonstrated the ability to reinforce the performance of several therapeutic modalities, including photodynamic therapy (PDT), photothermal therapy (PTT), chemodynamic therapy (CDT), and sonodynamic therapy (SDT), while also serving as efficient carriers for targeted drug release. Their structural versatility further enables improved drug stability, enhanced solubility, and controlled-release behavior. This review provides an overview of recent progress in MOF-enabled therapeutic strategies and discusses their potential applications in the treatment of HCC.