Spatiotemporal controlled disintegration enabling injected magnetic hydrogel for percutaneous hepatocellular carcinoma treatment.

Disintegrating hydrogels offer the advantages of synergistically enhancing therapeutic efficacy in locoregional percutaneous treatment for early hepatocellular carcinoma, enabling on-demand drug delivery with reduced side effects. However, current disintegration processes suffer from limited precise control and weak tissue penetration. Herein, we constructed an injectable ferrimagnetic hydrogen bonding cross-linked hydrogel (named as FPH) as a locoregional percutaneous agent by integrating ferrimagnetic nanoparticles into a polyvinyl alcohol (PVA) crosslinked network. This hydrogel enables remote magnetothermally triggered disintegration under an alternating magnetic field (AMF), with its disintegration temperature precisely tunable by adjusting the hydrogel's solid content. Under magnetic heating effect, FPH achieved remote "gel to disintegration" behavior at a desired temperature range of around 47 °C, effectively suppressing tumor cells and minimizing harm to normal tissues. By contrast, other commonly used hydrogen-bonded network of gelatin hydrogel disintegrated below body temperature or agarose hydrogel disintegrated over 70 °C. Benefiting from magnetothermal-controlled disintegration, drug-loaded FPH exhibited an increased release efficiency from ∼8 % (without AMF) to ∼45 % (with AMF) within 1 h. Following ultrasound-guided percutaneous delivery, FPH exhibited synergistic efficacy with magnetic hyperthermia and disintegration-mediated chemotherapy in rabbit liver tumors. Additionally, FPH is fabricated using clinically approved pharmaceutical excipients, ensuring excellent biocompatibility. This strategy inspires the design of spatiotemporally controllable disintegrating hydrogels with limitless tissue penetration depth, and expands their potential in percutaneous hepatocellular carcinoma treatment.