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

Abstract

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.

Keywords:

• TME-responsive
• cascade catalytic nanoreactor
• nano hydrogel
• phase transition
• starvation treatment
• •OH

Disclosure statement

The authors declare no competing financial interest.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (82102918) and the Youth Talent Promotion Project in Henan Province (2020HYTP011).