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 (1O2) 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.

Stimuli Responsive Nitric Oxide-Based Nanomedicine for Synergistic Therapy

“…In animal experiments, the bioluminescent imaging signal intensity in mice treated with this method showed a significant increase in the efficiency of tumor growth inhibition of up to 60% (Figure 4D) [86]. In addition to PTT, PDT is also an effective approach to trigger the release of NO [143]. PDT involves NIR stimulating the photosensitive material, which transfers energy to the surrounding tissues to produce a large number of reactive ROS [144,145].…”

“…In addition to PTT, PDT is also an effective approach to trigger the release of NO [143]. PDT involves NIR stimulating the photosensitive material, which transfers energy to the surrounding tissues to produce a large number of reactive ROS [144,145].…”

Novel gas‐based nanomedicines for cancer therapy

“…(D) Palladium nanocrystal‐engineered metal‐organic frameworks for synergistic hydrogen/photodynamic therapy. Reproduced with permission 159 . Copyright 2021, Wiley‐VCH.…”

“…Recently, Zhu and co‐workers have designed a nanoscale porphyrin MOF integrated with nanopalladium crystals for synergistic hydrogen/PDT (Figure 6D). 159 Hence, H 2 is particularly prospective for tumor therapy as a tumor‐specific therapeutic gas.…”

Versatile Nanoscale Metal–Organic Frameworks (nMOFs): An Emerging 3D Nanoplatform for Drug Delivery and Therapeutic Applications

“…also reported the construction of biocompatible palladium nanocrystals‐engineered PCN‐224 for synergistic hydrogen/PDT with enhanced cancer inhibition capability. [ 110 ]…”