Disphosphate based hydrogel microspheres for targeted transarterial radioembolization and chemoembolization therapies

Transarterial radioembolization (TARE) is a highly effective treatment for unresectable hepatocellular carcinoma (HCC). However, current clinically available radioactive ⁹⁰Y resin microspheres face significant challenges such as isotope leakage and low specific activity, compromising the safety and therapeutic efficacy.

To address these challenges, we propose a novel diphosphonate based hydrogel microspheres (DPMs) for safer and more effective TARE therapies. The diphosphonate have a strong chelating capability with various metal ions which provide a universal strategy for tightly labelling the hydrogel microsphere with different therapeutic metal nuclides.

In this study, DPMs were fabricated via microfluidic technology, followed by ¹⁷⁷Lu radiolabeling and doxorubicin (DOX) loading. Physicochemical characterization, radiostability assays, and dual-modality therapeutic efficacy were systematically evaluated in vitro and in orthotopic HCC rabbit models, with biosafety validated through histopathology and serum biochemistry.

DPMs achieved a labeling efficiency of 98.3 % within 15 min. Meanwhile, the radiolabeling rate maintained 99 % over 7 days in a 10 % fetal bovine serum solution, demonstrating exceptional radiostabilty. The high in vitro radiostability is also consistent with in vivo experiments. Additionally, the porous structure of DPMs enables high loading and controlled release of chemotherapeutic drugs, making the hydrogel microspheres also the ideal carriers for transcatheter arterial chemoembolization (TACE). By combining TARE and TACE, we have developed a novel ¹⁷⁷Lu-DPMs@DOX platform, exhibiting remarkable therapeutic performance against HCC without any observed side effect.

This study introduces a groundbreaking approach using highly effective diphosphonate based microspheres to deliver precise, safe, and powerful treatment for unresectable HCC and other challenging tumors.