Scientists have recently developed multifunctional hexagonal Na_xWO₃ nanocrystals that can serve as microwave sensitizers to kill cancer cells as well as improve the overall chemodynamic therapy (CDT). This study is available as a pre-proof in Chemical Engineering Journal.

Technologies Associated with Clinical Management of Tumors​​​​​​​

Some of the thermal ablation technologies, such as radiofrequency ablation (RFA) and microwave ablation (MWA), have been popularly used for the clinical management of tumors. Compared to conventional therapies, thermal ablation therapies involve minimal invasion, shorter duration of hospitalization, lower mortality rate and reduced cost of therapy.

Over the years, MWA has become an alternative method to RFA, because of its higher heating efficiency, deep penetration and, large ablation area. MWA is based on hyperthermia, i.e., above 60℃, which can cause denaturation of protein and, thereby, cause irreversible cellular injury. Importantly, researchers observed that MWA therapy was effective against primary or metastatic tumors associated with lung cancer, liver cancer and breast cancer.

Two of the key limitations of MWA therapy include uneven distribution of heat and quick diffusion; these lead to damaging both malignant as well as surrounding healthy tissues. To overcome this drawback, scientists have developed various microwave sensitizers that can transform microwave electromagnetic energy into thermal energy and accumulate maximum heat at the target site.

Chemodynamic therapy (CDT) is an emerging anticancer therapy based on a Fenton/Fenton-like reaction that produces highly oxidative hydroxyl radicals in cancer cells. However, the development of CDT as a sole cancer treatment has not been possible due to some limitations, such as insufficient catalytic efficiency and unfavorable reaction conditions. Scientists stated that enhancement of temperature could be an effective strategy to improve Fenton/Fenton-like reactions. To date, all the approaches have been based on a photothermal enhancement of CDT, providing an unfavorable low penetration rate for clinical application.

Potential of Hexagonal Tungsten Oxide Nanomaterials for Cancer Therapy

Nanomaterials of tungsten oxide and tungsten bronzes are known to be less toxic, possess many unique properties, and are multifarious crystal structures. Scientists were curious to explore its potential for microwave heating due to some characteristic features of hexagonal tungsten oxide nanomaterials, e.g., large surface area, ions intercalation ability, and tunneled structure. Additionally, the introduction of cations into tungsten oxide makes it a favorable candidate for CDT.

Scientists believe that the combination of CDT and MWA could be an efficient cancer treatment strategy. Keeping this in mind, researchers of the current study thought that exploring flexible redox states of the W element (W⁵⁺/W⁶⁺) could be ideal for developing a novel W-based nanocrystal required for synergistic antitumor therapy.

In this study, researchers developed hexagonal phase Na_xWO₃ nanocrystals via hydrothermal processes. These nanocrystals were analyzed for their efficiency as microwave sensitizers as well as a nano-catalyst for microwave thermal-enhanced CDT.

Scientists characterized the newly developed Na_xWO₃ nanocrystals via scanning electron microscope (SEM), which revealed the presence of rod-shaped nanostructures of 100-150 nm length and 100-150 nm diameter. Researchers observed that cationic ions could readily occupy these hexagonal tunneled nanostructures, which hinted at its potential as a microwave thermal sensitizer. Additionally, the incorporation of polyvinylpyrrolidone (PVP) on the surface of Na_xWO₃ nanostructures was confirmed via FT-IR analysis. In this study, researchers revealed that PVP-modified Na_xWO₃ nanorods possessed significant biocompatibility and dispersibility.

Scientists reported that both in vitro and in vivo studies revealed that newly synthesized Na_xWO₃ nanocrystals exhibited promising thermal effects when subjected to microwave irradiation. This might be due to its tunneled structure and ions intercalation properties that promote the trapping of more ions/polar molecules vibrating in a confined space. Additionally, the flexibly reversible redox nature of W elements allows Na_xWO₃ nanocrystals to degrade endogenous H₂O₂ into highly active hydroxyl radical through a Fenton-like reaction. Subsequently, via the redox process, Na_xWO₃ nanocrystals can also consume the reduced substances, i.e., glutathione (GSH).

Importantly, the high concentration of hydroxyl radical and low level of GSH in the malignant cells, instead of healthy tissues, facilitate selective inhibition of tumor cells via mitochondrial dysfunction, elicited by reactive oxygen species (ROS). Another advantage of this approach has been the application of hyperthermia associated with MWA, which can not only trigger coagulative necrosis in malignant cells but also enhance ROS generation by increasing the catalytic efficiency of Na_xWO₃ nanocrystals via a Fenton-like reaction.

In this study, researchers also studied the efficacy of Na_xWO₃ nanocrystals in killing cancer cells using 4T1 cells and HUVEC cells. This study showed that an increase in the concentration of Na_xWO₃ nanocrystals enhanced cytotoxicity on 4T1 cells, and decreased its viability by 67.8%. This result implies the potential of Na_xWO₃ nanocrystals in inhibiting the growth of cancer cells without affecting healthy cells (HUVEC cells).

Conclusion​​​​​​​

The authors of this study stated that the newly synthesized Na_xWO₃ nanocrystals, with promising microwave heating ability, improved catalytic performance, and biocompatibility could be effectively applied for antitumor therapy.