Oxygen Self‐Supply Engineering‐Ferritin for the Relief of Hypoxia in Tumors and the Enhancement of Photodynamic Therapy Efficacy
Yang Zhu, Duo Jin, Manman Liu, Yi Dai, Li Li, Xinwei Zheng, Lulu Wang, Aizong Shen, Jianing Yu, Sisi Wu, Yun Wu, Kai Zhong, Junjie Cheng, Yangzhong Liu
Abstract
Abstract 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 MnO 2 core in an engineered ferritin (Ftn), generating a nanozyme promoted PDT nanoformula (Ce6/Ftn@MnO 2 ) for tumor therapy. Ce6/Ftn@MnO 2 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@MnO 2 in the tumors of mice, and the treatment significantly decreases the expression of hypoxia‐inducible factor (HIF)‐1α. The Ce6/Ftn@MnO 2 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 H 2 O 2 in TME significantly enhances the r 1 relativity of Ce6/Ftn@MnO 2 , 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.