Advanced Materials Significant progress!

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iNature Chemokinetic Therapy (CDT) uses Fenton's catalyst to kill cancer cells by converting hydrogen peroxide (H2O2) in cells into hydroxyl radicals (OH-).

Although many studies have been conducted on H2O2 supplementation to improve the therapeutic effect of CDT, few studies have focused on superoxide radicals (O2-•).

In the application of CDT, this may lead to better efficacy.

One of the main problems with O2-•mediated CDT is that it easily induces severe oxidative damage to normal tissues, which can be solved by using a degradable O2-• scavenger.

On May 29, 2021, Jiang Hulin and other research teams from China Pharmaceutical University published a research paper entitled "A Harmless–Harmful Switchable and Uninterrupted Laccase-Instructed Killer for Activatable Chemodynamic Therapy" on Advanced Materials (IF=27.
40) online , Constructed a harmless-harmful switchable and uninterrupted laccase (LAC) induction reagent (HULK), which is the first CDT agent induced by LAC to accelerate the production of O2-•, and due to O2- • The photodegradation of the scavenger FeCe6 has a harmless-harmful switchable effect.

In conclusion, this work not only provides the first strategy for O2−• generation guided by LAC, but also provides new insights into activatable CDT.

Chemodynamic therapy (CDT) is an emerging cancer treatment strategy that uses Fenton/Fenton-like reactions to induce apoptosis and necrosis.

In the Fenton reaction, transition metal ions catalyze the decomposition of hydrogen peroxide (H2O2) into hydroxyl radicals (OH-), which are the most harmful reactive oxygen species (ROS).

It is considered to be the most critical step in this process, because the reaction of Fe3+ and Fe2+ is the most critical step in the process, because the reaction of H2O2 and Fe3+ is much slower than the reaction between H2O2 and Fe3+.

However, due to the relatively high pH, ​​the low concentration of endogenous H2O2 and the high expression of reducing substances in the tumor site, it is difficult to treat malignant tumors.

It is very difficult to use CDT alone to treat malignant tumors.

CDT is used alone to treat malignant tumors.

In order to improve the therapeutic effect of CDT, many strategies, such as increasing local H2O2 production, lowering tumor pH and reducing glutathione (GSH) levels, have been explored to improve the therapeutic effect of CDT.

In order to successfully apply this strategy in CDT, laccase (LAC) was introduced for the first time to continuously generate O2-.

Laccase is a copper-containing oxidase that oxidizes substrates (such as phenols and aliphatic or aromatic amines) with one electron to generate corresponding free radicals.

In particular, it is reported that OH- is produced in fungi through the redox cycle of quinone.

LACs oxidizes 2-methoxy-1,4-benzohydroquinone or QH2 to semiquinone radicals (methoxysemiquinone, QH-), QH- reduces O2 to produce perhydroxyl radicals (HOO-) and Their conjugate base O2--, they can be decomposed to produce H2O2.

 In addition, HOO-/O2-- can effectively reduce Fe3+ and generate additional Fe2+.

Through these LAC guidelines, a complete Fenton reaction system can be produced to overcome the limitation of insufficient reactants.

In addition, quinones can be reduced to hydroquinones by nicotinamide adenine by nicotinamide adenine dinucleotide phosphate (NADPH)-dependent reductase under physiological conditions.

Therefore, an LAC-guided self-circulation system is completed, leading to active and uninterrupted O2-•generation.

Unfortunately, the uninterrupted O2-• production and non-selective damage are very toxic to normal tissues and ultimately lead to adverse health effects.

Therefore, in order to eliminate the excessive O2-•by-products in normal tissues, FeCe6, which has superoxide dismutase mimic activity and catalysis, was introduced into the system.

At the same time, as a photosensitizer derivative, FeCe6 is easily degraded by light and can be used in this activatable system.

In short, this research not only provides the first strategy for O2-•generation guided by LAC, but also provides new insights into activatable CDT.

Reference message: https://onlinelibrary.
wiley.
com/doi/10.
1002/adma.
202100114 —END—