Researchers at Jinan University in Guangzhou, China have reported a thermotropic hydrogel tumor therapy platform that exploits the fatty acid-rich environment of surgical resection cavities to induce ferroptosis in residual cancer cells while simultaneously reprogramming immunosuppressive macrophages, according to a study published June 18, 2026 in Cell Reports Medicine. The findings suggest that the lipid-rich tumor microenvironment left behind after surgery — typically regarded as a barrier to immune clearance — can be redirected as a therapeutic substrate.
Postsurgical recurrence remains a major challenge in solid tumors, as residual cancer cells and an immunosuppressive microenvironment can promote regrowth even after apparently complete resection. To address this, the researchers developed LTG@RL, a near-infrared-responsive hydrogel designed to conform to irregular surgical cavities and provide sustained local drug delivery.
The platform combines a thermotropic hydrogel with a nanomodulator containing lipoxygenase (LOX) and rapamycin. LOX converts fatty acids within the tumor microenvironment into lipid peroxides that trigger ferroptosis, while rapamycin suppresses cellular antioxidant defenses and promotes macrophage polarization toward a pro-inflammatory, anti-tumor state. Together, the components are intended to eliminate residual tumor cells while reversing local immune suppression.
The study was conducted in preclinical melanoma and breast cancer models, including postsurgical recurrence settings. In melanoma cells, LOX-induced lipid peroxidation produced ferroptosis under fatty acid-rich conditions. In macrophages, rapamycin reduced lipid accumulation and increased expression of pro-inflammatory markers while suppressing markers associated with immunosuppressive M2 macrophages.
In mouse models, the full LTG@RL plus near-infrared treatment produced the strongest suppression of tumor recurrence compared with control groups. Anti-tumor activity was observed in both postsurgical melanoma and breast cancer models, as well as in an orthotopic melanoma model. Transcriptomic analyses supported activation of ferroptosis pathways and macrophage reprogramming, while safety studies found no significant body weight loss or major organ toxicity.