Radiofrequency enhances drug release from responsive nanoflowers for hepatocellular carcinoma therapy

Hepatocellular carcinoma (HCC) is the sixth most common malignant tumor and the third leading cause of cancer death worldwide. Most patients are diagnosed at an advanced stage, and systemic chemotherapy is the preferred treatment modality for advanced HCC. Curcumin (CUR) is a polyphenolic antineoplastic drug with low toxicity obtained from plants. However, its low bioavailability and poor solubility limit its functionality. In this study, radiofrequency- (RF) enhanced responsive nanoflowers (NFs), containing superparamagnetic ferric oxide nanoclusters (Fe₃O₄ NCs), - CUR layer, - and MnO₂ (CUR-Fe@MnO₂ NFs), were verified to have a thermal therapeutic effect. Transmission electron microscopy was used to characterize the CUR-Fe@MnO₂ NFs, which appeared flower-like with a size of 96.27 nm. The in vitro experimental data showed that RF enhanced the degradation of CUR-Fe@MnO₂ NFs to release Mn²⁺ and CUR. The cytotoxicity test results indicated that after RF heating, the CUR-Fe@MnO₂ NFs significantly suppressed HCC cell proliferation. Moreover, CUR-Fe@MnO₂ NFs were effective T ₁/T ₂ contrast agents for molecular magnetic resonance imaging due to the release of Mn²⁺ and Fe₃O₄ NCs.