Enhanced Photodynamic Therapy by Reduced Levels of Intracellular Glutathione Obtained By Employing a Nano‐MOF with Cu^II as the Active Center

Abstract

In photodynamic therapy (PDT), the level of reactive oxygen species (ROS) produced in the cell directly determines the therapeutic effect. Improvement in ROS concentration can be realized by reducing the glutathione (GSH) level or increasing the amount of photosensitizer. However, excessive amounts photosensitizer may cause side effects. Therefore, the development of photosensitizers that reduce GSH levels through synergistically improving ROS concentration in order to strengthen the efficacy of PDT for tumor is important. We report a nano-metal-organic framework (Cu -metalated nano-MOF {CuL-[AlOH] } (MOF-2, H L=mesotetrakis(4-carboxylphenyl)porphyrin)) based on Cu as the active center for PDT. This MOF-2 is readily taken up by breast cancer cells, and high levels of ROS are generated under light irradiation. Meanwhile, intracellular GSH is considerably decreased owing to absorption on MOF-2; this synergistically increases ROS concentration and accelerates apoptosis, thereby enhancing the effect of PDT. Notably, based on the direct adsorption of GSH, MOF-2 showed a comparable effect with the commercial antitumor drug camptothecin in a mouse breast cancer model. This work provides strong evidence for MOF-2 as a promising new PDT candidate and anticancer drug.

Photo‐Fenton‐like Metal–Protein Self‐Assemblies as Multifunctional Tumor Theranostic Agent

“…Importantly, the PDT effect is directly determined by intracellular reactive oxygen species (ROS) level . However, the overexpressed glutathione (GSH) in tumor cells usually tend to destroy the ROS production resulting in poor PDT effect . Furthermore, the hypoxia in tumor microenvironment is also a major obstacle .…”

Single‐Atom Catalysts in Catalytic Biomedicine

“…β‐Lap was utilized as ROS generator as it could be activated in HeLa cells to rapidly produce ROS . The in situ ROS production by β‐Lap administration and ROS scavenging by Fe‐SAs/NC were assessed by using a fluorescent ROS assay . The capability of Fe‐SAs/NC in protecting cellular oxidative stress was confirmed by evaluating the cellular ROS level of β‐Lap‐stimulated HeLa cells in the presence and absence of Fe‐SAs/NC (Figure f).…”

Nanoscale Metal‐Organic Frameworks: Synthesis, Biocompatibility, Imaging Applications, and Thermal and Dynamic Therapy of Tumors

“…Then various targeted molecules can be coupled with large numbers of chemical groups on the surface of NMOFs. Considering the advantages of NMOFs in structural diversity and high specific surface area, kinds of photosensitizers can arrange periodically in the NMOF framework, which can not only effectively avoid the self‐aggregation and self‐quenching of photosensitizer, but also solve the water‐soluble problems . In addition, the porous structure not only promotes the diffusion of ROS, and ultimately increases the yield of PDT, but also can load a lot of functional molecules for further effective treatment .…”

“…At last, the achieved tumor regression rate was more than 98%, and the cure rate was up to 60%. In addition to thinking about it from the hypoxic point of view, the combination of many other aspects has also become a hot topic of inquiry, such as the use of high levels of GSH and hydrogen sulfide (H 2 S) in tumors, and the weak acidity in tumor microenvironment . Zhang and co‐workers have also proposed a novel work by utilizing this idea, in which Mn‐NMOFs could be reduced by GSH in tumor, then the released Mn(II) and TCPP could be used for MRI and PDT.…”