Nano-radiosensitization has been a hot concept for the past ten years, and the nanomaterial-mediated tumor radiosensitization method is mainly focused on increasing intracellular radiation deposition by high atomic number (high Z) nanomaterials, particularly gold (Au)-mediated radiation enhancement. Recently, various new nanomaterial-mediated radiosensitive approaches have been successively reported, such as catalyzing reactive oxygen species (ROS) generation, consuming intracellular reduced glutathione (GSH), overcoming tumor hypoxia, and various synergistic radiotherapy ways. These strategies may open a new avenue for enhancing the radiotherapeutic effect and avoiding its side effects. Nevertheless, reviews systematically summarizing these newly emerging methods and their radiosensitive mechanisms are still rare. Therefore, the general strategies of nanomaterial-mediated tumor radiosensitization are comprehensively summarized, particularly aiming at introducing the emerging radiosensitive methods. The strategies are divided into three general parts. First, methods on account of the intrinsic radiosensitive properties of nanoradiosensitizers for radiosensitization are highlighted. Then, newly developed synergistic strategies based on multifunctional nanomaterials for enhancing radiotherapy efficacy are emphasized. Third, nanomaterial-mediated radioprotection approaches for increasing the radiotherapeutic ratio are discussed. Importantly, the clinical translation of nanomaterial-mediated tumor radiosensitization is also covered. Finally, further challenges and outlooks in this field are discussed.

Emerging Strategies of Nanomaterial-Mediated Tumor Radiosensitization.

Radiotherapy is one of the major therapeutic strategies for cancer treatment. In the past decade, there has been growing interest in using high Z (atomic number) elements (materials) as radiosensitizers. New strategies in nanomedicine could help to improve cancer diagnosis and therapy at cellular and molecular levels. Metal-based nanoparticles usually exhibit chemical inertness in cellular and subcellular systems and may play a role in radiosensitization and synergistic cell-killing effects for radiation therapy. This review summarizes the efficacy of metal-based NanoEnhancers against cancers in both in vitro and in vivo systems for a range of ionizing radiations including gamma-rays, X-rays, and charged particles. The potential of translating preclinical studies on metal-based nanoparticles-enhanced radiation therapy into clinical practice is also discussed using examples of several metal-based NanoEnhancers (such as CYT-6091, AGuIX, and NBTXR3). Also, a few general examples of theranostic multimetallic nanocomposites are presented, and the related biological mechanisms are discussed.

Metal-based NanoEnhancers for Future Radiotherapy: Radiosensitizing and Synergistic Effects on Tumor Cells.

Thiol-capped Bi nanoparticles as stable and all-in-one type theranostic nanoagents for tumor imaging and thermoradiotherapy.

Multifunctional Magnetic Gold Nanomaterials for Cancer.

NIR-II reinforced intracellular cyclic reaction to enhance chemodynamic therapy with abundant H2O2 supply.

Imaging guided combined therapy has attracted great attention in recent years. This study develops core–shell Au@FeS nanoparticles with polyethylene glycol (PEG) coating as multifunctional nanotheranostic agent for tumor imaging and combined photothermal therapy (PTT) and radiotherapy (RT). In this Au@FeS nanostructure, the gold core can act as a radiosensitizer for enhanced RT, while FeS shell offers contrast for T2-weighted magnetic resonance imaging and endows the nanoparticles with strong high near-infrared (NIR) for photoacoustic imaging and PTT. As demonstrated by both in vitro and in vivo experiments, Au@FeS-PEG can act as excellent therapeutic agent for cancer synergistic treatment. More importantly, mild PTT boosts the blood flow into tumor and increases oxygenation to overcome the tumor hypoxia microenvironment, further enhancing the efficacy of RT. Moreover, Au@FeS-PEG induces on obvious toxicity at a high dose (20 mg kg−1) to the treated mice as evidenced by blood biochemistry. Therefore, this study brings an excellent strategy for cancer enhanced RT through NIR-triggered mild PTT to overcome hypoxia-associated radioresistance.

Synergistic Effect of Thermo‐Radiotherapy Using Au@FeS Core–Shell Nanoparticles as Multifunctional Therapeutic Nanoagents


 In the archive of the Ground Wide Angle Camera (GWAC), we found 43 white light flares from 43 stars, among which, three are sympathetic or homologous flares, and one of them also has a quasi-periodic pulsation with a period of $13.0\pm1.5$ minutes. Among these 43 flare stars, there are 19 new active stars and 41 stars that have available TESS and/or \textit{K2} light curves, from which we found 931 stellar flares. We also obtained rotational or orbital periods of 34 GWAC flare stars, of which 33 are less than 5.4 days, and ephemerides of three eclipsing binaries from these light curves. Combining with low resolution spectra from LAMOST and the Xinglong 2.16m telescope, we found that $L_{\rm H\alpha}/L_{\rm bol}$ are in the saturation region in the rotation activity diagram. From the LAMOST medium-resolution spectrum, we found that Star \#3 (HAT 178-02667) has double H$\alpha$ emissions which imply it is a binary, and two components are both active stars. Thirteen stars have flare frequency distributions (FFDs) from TESS and/or \textit{K2} light curves. These FFDs show that the flares detected by GWAC can occur at a frequency of 0.5 to 9.5\,yr$^{-1}$. The impact of flares on habitable planets was also studied based on these FFDs, and flares from some GWAC flare stars may produce enough energetic flares to destroy ozone layers, but none can trigger prebiotic chemistry on their habitable planets.

/pdf/magnetic-activity-and-parameters-of-43-flare-stars-in-the-2ha8sms4.pdf

Magnetic activity and parameters of 43 flare stars in the GWAC archive

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Synergistic Effect of Thermo‐Radiotherapy Using Au@FeS Core–Shell Nanoparticles as Multifunctional Therapeutic Nanoagents

Magnetic activity and parameters of 43 flare stars in the GWAC archive