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

Linyu Gaoa, Xiangyang Xuana, Mingli Suia, Jingjing Wanga, Yaping Wanga & Huijuan Zhangabc*a School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Chinab Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Zhengzhou, Henan Province, Chinac Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou, Henan Province, ChinaSupplemental data for this article can be accessed here.CONTACT Huijuan Zhang zhanghuijuan4@163.com No.100, Kexue Road, Zhengzhou, 450001, P. R. ChinaAbstractThe 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.