Supramolecular Gels with Controllable Degradation for Suppressing Tumor
Recurrence and Relieving Postoperative Pain
Abstract
Postoperative pain and tumor recurrence are critical challenges
following malignant tumor resection. To address these issues, we
developed a supramolecular gel delivery system loaded with ropivacaine
microcrystals (RopC Gel). Using PEG400 as the solvent, we successfully
screened and identified matrix materials capable of forming
supramolecular hydrogels through a heating-cooling process. By
strategically leveraging the hydrophilic and hydrophobic properties of
the gel matrix, we controlled its mechanical strength and degradation
rate by adjusting the ratio of hydrophilic to hydrophobic components,
resulting in a degradable, injectable, and self-healing gel delivery
system. In both rat plantar incision and mouse tumor resection pain
models, RopC Gel provided long-lasting analgesia for up to five days.
Notably, tumor-resected mice treated with RopC Gel demonstrated extended
survival and slower tumor progression. Further in vitro and in vivo
experiments revealed that RopC Gel affects mitochondrial function by
promoting the accumulation of reactive oxygen species in tumor cells,
inducing pyroptosis, stimulating immunogenic cell death (ICD), and
activating anti-tumor immune responses. This work offers an innovative
solution for postoperative tumor resection management. Additionally, the
controllable degradation properties outlined in this study provide an
efficient strategy for the controlled release of multiple drugs, with
potential for widespread clinical applications.