"Nanocapsules" Provide New Solution For Efficient Cancer Chemodynamic Therapy

Mar 14, 2022 | By QIAN Yong, ZHAO Weiwei

In a paper published on Small recently, a collaborated research team led by Prof. WANG Hui from High Magnetic Field Laboratory, Hefei Institutes of Physical Science (HFIPS), Chinese Academy of Sciences (CAS) reported the synthesis of hollow cuprous oxide@nitrogen-doped carbon (HCONC) by one-step hydrothermal method as well as their applications in efficient chemodynamic therapy.

In recent years, chemodynamic therapy (CDT) responsive to tumor microenvironment (TME) has received extensive attention due to its low invasiveness and high selectivity. Among various metal-based nanocatalysts, the low redox potential of Cu+/Cu2+ in cuprous-based nanocatalysts endows them with higher reactive oxygen species (ROS) yields and reduced glutathione (GSH) overexpression, which can also be shown great promise as a Fenton-like agent under relatively loose conditions. However, the susceptibility to oxidation and potential ionic toxicity of cuprous-based nanocatalysts severely limit their applications in nanomedicine. Therefore, it is necessary to develop a cuprous-based nanocatalyst with good biocompatibility to deplete the overexpression of GSH to enhance CDT.

In this research, researchers used a one-step hydrothermal method to synthesize HCONC nanocapsules for catalysing the cascade reaction and improving the efficacy of CDT. This "nanocapsules" composed of nanoparticles is not "capsules" in the traditional sense. It is a core-shell structure formed by ingeniously attaching a thin layer of carbon to the surface of hollow cuprous oxide (Cu2O) nanocrystals, which not only effectively prevents the oxidation of Cu+, but also increases stability of Cu2O nanocrystals.

The Cu+-mediated Fenton-like reaction in HCONC can efficiently catalyze H2O2 to generate ·OH, and the Cu+ released in the TME can also decompose overexpressed GSH to protect nascent ROS.

Both in vitro and in vivo experiments show that HCONC has excellent antitumor ability without causing systemic toxicity. "The whole process can be described in a old saying," added Prof. WANG, "as the medicine took effect, the symptoms lessened."

The work was supported by the National Key R&D Program of China (Grant No. 2021YFA1600202), National Natural Science Foundation of China (U2032162, U1932158 and 81871085), Hefei Municipal Natural Science Foundation (2021009), Natural Science Foundation of Shandong Province (ZR2019LZL018), High Magnetic Field Laboratory of Anhui Province (AHHM-FX-2021-04), Project of Postdoctoral Science Foundation of China (2019M652403), and Project of Postdoctoral Innovation of Shandong Province (202002048). A portion of this work was performed on the Steady High Magnetic Field Facilities (SM1 superconducting magnet), High Magnetic Field Laboratory, Chinese Academy of Sciences.

Schematic illustration of HCONC-catalyzed cascade reaction for chemodynamic oncotherapy. (Image by WANG Hui)

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