Hyperbranched Poly(citric acid) Mitigated Iron Overload Damage via Iron Chelation and Antioxidation

Iron overload (IO) is a condition of excessive iron deposition in various organs, which can cause pathological changes. In the treatment of IO, iron chelators have toxic side effects, and antioxidants cannot decrease iron deposition. Herein, a biodegradable hyperbranched poly(citric acid) (PCA) was synthesized, and the therapeutic effects of PCA on IO were investigated based on liver and bone tissue iron injury mouse models. The results showed that PCA exerted good iron chelation abilities and inhibited iron overload-induced apoptosis, ROS production, and mitochondrial dysfunction. The bone loss model and liver injury model of mice revealed the potential of PCA in iron overload treatment. PCA reduced iron deposition in bones and improved bone tissue morphology and microstructure. Moreover, PCA inhibited the oxidative stress level, thereby reducing the degree of liver injury. In summary, these findings suggested that PCA could be a promising candidate for treating iron overload disorders.