Abstract

AbstractRadioactive microspheres have shown excellent therapeutic effects in the treatment of advanced hepatocellular carcinoma (HCC) due to indiscriminate embolization and killing of tumor cells. However, limitations such as unstable loading, in vivo reflux, and untrackable radioactive microspheres restrict their clinical applicability. Herein, a novel injectable lutetium‐177‐labeled 3D hollow porous radio‐granular hydrogels with a double‐cross‐linked network (177Lu‐3D‐HPGH) are synthesized via microfluidics combined with ultraviolet photo‐cross‐linking technology is reported. The radiolabeling efficiency of 177Lu‐3D‐HPGH can reach 97.85%. The 3D hollow porous radio‐granular hydrogels exhibited uniform, controllable size, radio‐theranostics, and excellent underwater adhesion properties, avoiding unwanted radiation damage to non‐target organs. Particularly, the extended X‐ray absorption fine structure combined with the density functional theory calculation revealed the mechanism of 3D‐HPGH loading with 177Lu through Lu‐N/O coordination. Furthermore, rabbit orthotopic kidney and liver tumor models are used to verify the excellent embolization performance, radionuclide loading stability, anti‐reflux characteristics, anti‐tumor effect, and biosafety of 177Lu‐3D‐HPGH. Briefly, this facile, green, and safe synthesis strategy provides a superior choice for intravascular brachytherapy of HCC and has great application value and transformative potential in clinical diagnosis and treatment.

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