Oxygen Self-Supply Engineering-Ferritin for the Relief of Hypoxia in Tumors and the Enhancement of Photodynamic Therapy Efficacy

Hypoxia is a hallmark of the tumor microenvironment (TME) that promotes tumor development and metastasis. Photodynamic therapy (PDT) is a promising strategy in the treatment of tumors, but it is limited by the lack of oxygen in TME. In this work, an O-2 self-supply PDT system is constructed by co-encapsulation of chlorin e6 (Ce6) and a MnO2 core in an engineered ferritin (Ftn), generating a nanozyme promoted PDT nanoformula (Ce6/Ftn@MnO2) for tumor therapy. Ce6/Ftn@MnO2 exhibits a uniform small size (15.5 nm) and high stability due to the inherent structure of Ftn. The fluorescence imaging and immunofluorescence analysis demonstrate the pronounced accumulation of Ce6/Ftn@MnO2 in the tumors of mice, and the treatment significantly decreases the expression of hypoxia-inducible factor (HIF)-1 alpha. The Ce6/Ftn@MnO2 nanoplatform exerts a more potent anti-tumor efficacy with negligible damage to normal tissues compared to the treatment with free Ce6. Moreover, the weak acidity and the presence of H2O2 in TME significantly enhances the r(1) relativity of Ce6/Ftn@MnO2, resulting in a prominent enhancement of MRI imaging in the tumor. This bio-mimic Ftn strategy not only improves the in vivo distribution and retention of Ce6, but also enhances the effectiveness and precision of PDT by TME modulation.

Automated summary

In this study, a self-supply oxygen photodynamic nanomedicine system was constructed, which achieved tumor therapy by modulating the tumor microenvironment. This nanomedicine exhibited small size and high stability, leading to pronounced accumulation in the tumor, decreased expression of hypoxia-inducible factor, enhanced anti-tumor efficacy, and improved MRI imaging in the tumor.