Hypoxia-tropic nanozymes as oxygen generators for tumor-favoring theranostics

Oxygen deficiency is the main obstacle of hypoxia-related theranostics, thus this is a considerable amount of research focusing on the development of methods to supply oxygen by taking advantage of hypoxia-responsive properties of nanoparticles. However, strategies to properly penetrate hypoxic regions by the nanoparticles remains an unmet challenge. In this work, a biomimetic nanozyme capable of possessing catalase-like activity and the efficient direct penetration of hypoxic areas in tumor tissues was developed to supply oxygen based on catalytic tumor microenvironment-responsive reaction, providing substantial tumor hypoxia relief with nearly 3-fold reduction compared to untreated tumor tissues. To demonstrate the advantages of the nanozymes in overcoming hypoxia, a theranostic nanosystem model composed of the core/shell nanozymes and aggregation-induced emission (AIE) molecules was designed. The nanosystem was able to present multi-modal imaging of tumors and modulated the tumor microenvironment for improved photodynamic therapy (PDT) by cascade reactions of therapeutic effector molecules, thereby providing significantly enhanced therapeutic benefits in inhibiting tumor growth and lung metastasis of orthotopic breast cancer. This conceptual study showed the multifaceted features of biomimetic nanozymes as tumor therapeutics and demonstrated the encouraging potential for modulating hypoxia as an application for tumor theranostics.