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 Fe/Fe 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 circulation to avoid hypoglycaemia. When it reached the targeted tumour site, reductive GSH can reduce Fe to Fe. 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 HO generated by the reaction between GOx and Glu can be catalysed by Fe to produce highly cytotoxic •OH , which could further kill tumour cells. The 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 to achieve starvation-chemodynamic combined treatment for breast cancer.