Ruthenium‐Based Metal–Organic Nanoradiosensitizers Enhance Radiotherapy by Combining ROS Generation and CO Gas Release

Abstract

A lack of targeting accuracy and radiosensitivity severely limits clinical radiotherapy. In this study, we developed a radiosensitizer comprised of Ru-based metal-organic nanostructures (ZrRuMn-MONs@mem) to optimize irradiation by maximizing reactive oxygen species (ROS) generation and CO release in X-rayinduced dynamic therapy (XDT). The well-designed nanostructures increase the direct absorption of radiation doses (primary radiation) and promote the deposition of photons and electrons (secondary radiation). The secondary electrons were trapped and transferred in the constrained MONs where they induce a cascade of reactions to increase the therapeutic efficiency. Meanwhile, the full-length antiglypican 3 (GPC3) antibody (hGC33) expressed a cell membrane coating enabling active targeting of tumor sites with optimized biocompatibility. The ZrRuMn-MONs@mem represents a starting point for advancing an all-around radiosensitizer that operates efficiently in clinical XDT.

Zinc–Carnosine Metallodrug Network as Dual Metabolism Inhibitor Overcoming Metabolic Reprogramming for Efficient Cancer Therapy

“…As shown in Figure j, we further assessed the intracellular ROS production in 4T1 cells using a 2′,7′-dichlorofluorescin diacetates (DCFH-DA). , From the results, the Zn-Car MNs treated group showed a higher green fluorescence than the Zn 2+ treated group, suggesting that Zn-Car MNs produced more ROS within cancer cells.…”

Application of nanomedicine in radiotherapy sensitization

“…Dai et al. ( 43 ) developed a ruthenium-based metal-organic nanostructured radiotherapy sensitizer (ZrRuMn-MONs@mem) for the combined treatment of ROS and CO by increasing the direct absorption of radiation dose and facilitating the deposition of photons and electrons. In the present study, ruthenium metal-organic nanostructures show unique advantages in radiotherapy sensitization.…”

X-ray-responsive prodrugs and polymeric nanocarriers for multimodal cancer therapy

“…The X-ray-triggered generation of ˙OH and CO release from the nanoparticles were independent of oxygen, which induced remarkable therapeutic efficacy against both normoxic and hypoxic cancers. In another example, Liu et al 49 reported ZrRnMn-based metal–organic nanostructures for the combination of radiotherapy and gas therapy by maximizing the generation of reactive oxygen species (ROS) and CO release under X-ray radiation. Inside the nanoparticles, the Zr cluster absorbed X-rays, and Ru(bpy) 2 was activated for the production of ROS.…”