Radio-magnetic dual-functional microspheres for magnetic hyperthermia therapy combined with radioembolization of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) remains a formidable clinical challenge due to its aggressive nature, high recurrence rate, and limited therapeutic options, particularly for intermediate-advanced stage patients who are ineligible for surgical resection. Current transarterial chemoembolization (TACE) and conventional transarterial radioembolization (TARE) often face challenges such as incomplete tumor necrosis and radioresistance. To address these critical clinical issues, we develop an innovative polydopamine-coated ¹⁷⁷Lu-labeled magnetic microspheres (¹⁷⁷Lu-MMS@PDA) that synergistically combines TARE with magnetic hyperthermia therapy (MHT), which enable non-invasive, deep-tissue-penetrating hyperthermia while significantly enhancing radiostability. This dual-modality approach not only overcomes the limitations of single therapy but also demonstrates the unique clinical advantages including addressing the problem of uneven drug distribution in conventional embolization, overcoming tumor radioresistance and reducing off-target effects. Importantly, our large animal studies using beagle dogs have confirmed the outstanding biosafety profile of ¹⁷⁷Lu-MMS@PDA, meeting essential criteria for clinical translation. With its combined advantages of enhanced therapeutic efficacy and minimized systemic toxicity, ¹⁷⁷Lu-MMS@PDA represents a breakthrough solution for HCC treatment, particularly promising for patients with advanced or treatment-refractory disease.