Palladium Nanocrystals‐Engineered Metal–Organic Frameworks for Enhanced Tumor Inhibition by Synergistic Hydrogen/Photodynamic Therapy

Abstract Hydrogen therapy, as a star therapeutic modality, has recently acquired much attention in the field of anticancer medicine. Evidence suggests that hydrogen can selectively reduce intratumoral overexpressed hydroxyl radicals (•OH) to break the redox homoeostasis and thereby result in redox stress and cell damage. As a reactive oxygen species‐related noninvasive modality, photodynamic therapy (PDT) has been approved for varied tumor treatments clinically. For implementing tumor therapy with enhanced anticancer efficacy and attenuated side effects, here a biocompatible palladium nanocrystals‐integrated nanoscale porphyrinic metal–organic framework (NPMOF) is designed to develop a novel combined therapy modality, that is, synergistic hydrogen/photodynamic therapy. The NPMOF is employed simultaneously as the photosensitizer for PDT and as the nanocarrier to support palladium nanocrystals, which is further used as the hydrogen vehicle. The final hydrogen‐containing nanosystems exhibit a persistent reductive hydrogen release behavior and considerable light‐activated singlet oxygen ( 1 O 2 ) generation without mutual interference, contributing to the adequate disturbance of tumor microenvironment redox steady‐state for synergistically inducing tumor cell death. Ultimately, by coupling of tumor‐selective hydrogen therapy and PDT, the designed nanosystems realize the augmented therapeutic outcome with minimal side effects, providing a safe and efficient tumor treatment for future clinical translation.