Nanoreactor activated in situ for starvation-chemodynamic therapy of breast cancer

The nano-drug delivery system activated by the tumour microenvironment (TME) can effectively treat tumours with low toxicity. Based on a high level of reductive GSH in TME and the different coordination properties of Fe ions, this project intended to prepare a GSH-activated cascade catalytic nanoreactor for breast cancer treatment using Fe³⁺/Fe²⁺ as the molecular switch. In this study, the glucose oxidase (GOx) loaded iron alginate nano hydrogel (FeAlg/GOx) was prepared by the simple one-step titration method. Results showed that FeAlg/GOx could remain stable during in vivo circulation to avoid hypoglycaemia. When it reached the targeted tumour site, reductive GSH can reduce Fe³⁺ to Fe²⁺. Thereafter, FeAlg/GOx nanogel was broken and GOx was released to consume the essential nutrient glucose (Glu) to achieve tumour starvation therapy. Next, the substrate H₂O₂ generated by the reaction between GOx and Glu can be catalysed by Fe²⁺ to produce highly cytotoxic •OH in situ, which could further kill tumour cells. The in vivo pharmacodynamics results demonstrated that compared with the control group (V/V0 = 8.36 ± 1.73), FeAlg/GOx group showed the most significant anti-tumour effect with V/V0 of 3.08 ± 1.06. In conclusion, this "inactivated" FeAlg/GOx nanogel can be converted into "activated" therapeutic substances in situ to achieve starvation-chemodynamic combined treatment for breast cancer.