High-Performance Self-Cascade Pyrite Nanozymes for Apoptosis–Ferroptosis Synergistic Tumor Therapy

Abstract

As next-generation artificial enzymes, nanozymes have shown great promise for tumor catalytic therapy. In particular, their peroxidase-like activity has been employed to catalyze hydrogen peroxide (H 2 O 2 ) to produce highly toxic hydroxyl radicals ( • OH) to kill tumor cells. However, limited by the low affinity between nanozymes with H 2 O 2 and the low level of H 2 O 2 in the tumor microenvironment, peroxidase nanozymes usually produced insufficient • OH to kill tumor cells for therapeutic purposes. Herein, we present a pyrite peroxidase nanozyme with ultrahigh H 2 O 2 affinity, resulting in a 4144-and 3086-fold increase of catalytic activity compared with that of classical Fe 3 O 4 nanozyme and natural horseradish peroxidase, respectively. We found that the pyrite nanozyme also possesses intrinsic glutathione oxidase-like activity, which catalyzes the oxidation of reduced glutathione accompanied by H 2 O 2 generation. Thus, the dual-activity pyrite nanozyme constitutes a self-cascade platform to generate abundant • OH and deplete reduced glutathione, which induces apoptosis as well as ferroptosis of tumor cells. Consequently, it killed apoptosis-resistant tumor cells harboring KRAS mutation by inducing ferroptosis. The pyrite nanozyme also exhibited favorable tumor-specific cytotoxicity and biodegradability to ensure its biosafety. These results indicate that the high-performance pyrite nanozyme is an effective therapeutic reagent and may aid the development of nanozyme-based tumor catalytic therapy.

Network pharmacology and experimental investigation of Rhizoma polygonati extract targeted kinase with herbzyme activity for potent drug delivery

“…The correlation of fluorescence with phosphatase activity in anciently processed RP and 230 °C processed RP suggesting the characteristics of the nanoparticles correlate with the nanozyme/herbzyme activity of phosphatase. Compared to the metal-based nanozyme, this natural processed herbal nanozyme seems cost-effective and easily absorbs with potential in drug delivery (Meng et al, 2021 ).…”

Nanozymes in Tumor Theranostics

“…Nanoceria and iron oxide magnetic nanoparticles (Fe 3 O 4 MNPs) are the most widely utilized metal oxide catalysts among the metal oxide-based nanomaterials ( 5 , 8 – 10 , 16 , 34 , 35 ). Nanoceria exists in a mixed valence state (Ce 3+ and Ce 4+ ) ( 9 , 36 – 38 ).…”

Nano-evolution and protein-based enzymatic evolution predicts novel types of natural product nanozymes of traditional Chinese medicine: cases of herbzymes of Taishan-Huangjing (Rhizoma polygonati) and Goji (Lycium chinense)

“…Since the discovery of iron nanoparticles with intrinsic enzyme activity, more than 540 novel nanozymes have been reported with modifications since the first generation of nanozyme type of peroxidase by classical Fe 3 O 4 [3]. Recently Meng et al, for instance, reported an improved peroxidase of pyrite peroxidase nanozyme with super strong binding to substrate hydrogen peroxide (H 2 O 2 ) compared to traditional nanozyme Fe 3 O 4 and protein based horseradish peroxidase, with which additional glutathione oxidase-like activity, following with the catalysis of H 2 O 2 generation [4]. The dual nanozyme finally targeted KRAS mutation with tumor catalytic therapy [4].…”