Research On Ferroptosis-Based Synergistic Therapy Using Drug-Loaded Composite Hydrogel After Tumorectomy

Malignant tumor is a significant health concern,causing high mortality rates around the world.While surgical resection is the primary treatment option,postoperative chemotherapy and radiotherapy have been found to be ineffective,with serious systemic side effects.To improve treatment efficacy and limit recurrence,there is a pressing need to explore alternative therapies.Ferroptosis has been found to be an atypical form of cell death.Several studies have shown that tumor cells with high tumorigenic,aggressive and metastatic potential are sensitive to Ferroptosis.It is a feasible therapeutic strategy by promoting ferroptosis of tumor cells to preventing tumor recurrence.Combination therapies have shown promise in this area,and hydrogel carriers have emerged as an effective delivery mechanism for localized treatment.In this study,we explored multifunctional antitumor nanoparticles for postoperative treatment,utilizing different hydrogel carriers to deliver nanomedicines efficiently and precisely.Our approach aimed to tackle residual tumor tissues through multiple modalities,offering safe and effective treatment for patients.The research progress detailed in this paper provides a promising avenue for the development of more effective postoperative cancer treatment options.The research progress was shown as follows:The composite hydrogel was designed for the synergistic treatment of postoperative tumors with photodynamic/photothermal therapy/ferroptosis.Polyacrylic acid（PAA）and Pluronic F127（F127）were used to construct composite hydrogels for postoperative cancer treatment.Zinc centers containing carbon nano dodecahedron（ZCND）were prepared by high-temperature carbonization reaction,and ZCND and ferroptosis inducer erastin were loaded into the PAA:F127 hydrogel.Photothermal performance and reactive oxygen species generation tests showed that ZCND could enable photodynamic and photothermal therapies.It was also shown that the combined effect of photodynamic and photothermal therapies leads to a downregulation of intracellular heat shock protein（HSP70）expression,which reduces the stability of glutathione peroxidase 4（GPX4）and enhances the effect of erastin in activating ferroptosis.In addition,photodynamic and photothermal therapies generated large amounts of ROS to reduce glutathione of scavenge intracellular and increase intracellular oxidative stress,which led to promote tumor cell death.Animal experiments confirmed no obvious recurrence and death in tumor-removed mice after combined photodynamic,photothermal and erastin treatment.In vitro and in vivo experiments confirmed that ZCND-erastin/PAA:F127 hydrogel combined with photodynamic and photothermal treatment could effectively inhibit tumor recurrence after resection.Based on the previous chapter,a postoperative composite hydrogel for postoperative oncology was designed.The hydrogel is intended to provide synergistic photothermal therapy/ferroptosis treatment Magnetic carbonaceous porous composites（MCPC）were obtained by high-temperature carbon-based MOF（MIL-100（Fe））preparation.The MCPC was characterized by BET and the result showed it had a mesoporous structure for loading erastin.The qualitative analysis of MCPC by XRD and XPS showed that MCPC contained Fe₃O₄.Therefore,MCPC could provide an iron source for ferroptosis and increase iron accumulation to enhance ferroptosis effect.The photothermal conversion effect of MCPC was studied by using infrared thermography.Poly（dopamine）（PDA）and poly（acrylamide）（PAM）were used to construct a composite hydrogel for post-operative tumor treatment.PDA-PAM had the ability of self-healing,which led to wound repair at the tumor resection site.The hydrogel was shown to have excellent biosafety by MTT assay and two-dimensional cell growth assay.The cell survival of 4T1 tumor cells cultured under different conditions was also determined by MTT assay to evaluate the effective synergistic photothermal/ferroptosis treatment effect of erastin@MCPC.The results showed that the synergistic photothermal/ferroptosis therapy had significant anti-tumor effects.