An integrated multi-effect microsphere by body temperature assists for transcatheter arterial embolization in hepatocellular carcinoma

Aims To develop novel iodine alginate calcium microspheres (IACMs) with intrinsic radiopacity, embolic capability, and body-temperature-assisted iodine conversion for anti-tumor effects.Materials and methods IACMs were synthesized via Ca2+ crosslinking based on the I− + I2 = I3− equilibrium. Physicochemical characterization was performed. Radiopacity was assessed in vitro and in vivo using digital subtraction angiography and computed tomography (CT). Embolization efficacy was evaluated in rabbit ear artery, normal liver, and VX2 HCC models (n = 5 per group). Cell viability was assessed using a CCK-8 assay.Results IACMs achieved an encapsulation efficiency of 79.31% ± 2.08%, iodine loading rate of 44.78%. The median particle size (D50) was 176.6 µm. IACMs exhibited good X-ray visibility (in vivo/vitro) with CT attenuation of 4236 ± 48 HU. In the rabbit VX2 HCC model, IACMs produced sustained tumor hyperdensity with partial resolution of the lesion by day 7 (p < 0.001 vs control). In vitro, IACM extract reduced HepaRG and HepG2 cell viability to 8% and 10% at 72 h, respectively (p < 0.001), while direct contact showed no cytotoxicity (>98% viability).Conclusions IACMs integrate radiopacity, embolization, and temperature-assisted iodine conversion into a single platform, enabling real-time procedural guidance and noninvasive follow-up without exogenous contrast. IACMs show substantial potential for clinical translation in tumor embolization therapy.