Flower-like Nanozyme with Highly Porous Carbon Matrix Induces Robust Oxidative Storm against Drug-Resistant Cancer

Abstract

Reactive oxygen species (ROS) generators are sparking breakthroughs in sensitization and treatment of therapy-resistant tumors, yet the efficacy is drastically compromised by limited substrate concentrations, short lifetimes of free radicals, and restricted oxidative damage. Herein, a flower-like nanozyme with highly permeable leaflets accommodating catalytic metal sites was developed to address the challenges by boosting substrate and product accessibility. In the formation of a zeolite imidazole framework, cobalt ions promoted catalytic polymerization and deposition of polydopamine. The polymers acted as a stiffener for preventing framework collapse and maneuvering pore reopening during carbonization. The cobalt single-atom/cluster sites in the highly porous matrix generated peroxidase/oxidase-like activities with high catalytic efficiency (K cat/K m) up to 6 orders of magnitude greater than that of conventional nano-/biozymes. Thereby, a robust ROS storm induced by selective catalysis led to rapid accumulation of oxidative damage and failure of antioxidant and antiapoptotic defense synchronization in drug-resistant cancer cells. By synergy of a redox homeostasis disrupter co-delivered, a significantly high antitumor efficiency was realized in vivo. This work offers a route to kinetically favorable ROS generators for advancing the treatment of therapy-resistant tumors.

A Single NIR‐II Laser‐Triggered Self‐Enhancing Photo/Enzyme‐coupled Three‐in‐One Nanosystems for Breast Cancer Phototheranostics

“…The increased ratio of Bax/Bcl‐2 indicated that the PdCu NYs promoted apoptosis. [ 36 ] Moreover, after treatment with PdCu upon 1064 nm laser irradiation, the expression levels of caspase‐3 and caspase‐9's activated form (cleaved caspase‐3 and cleaved caspase‐9) were upregulated with a greater extent. Noteworthy, the colony efficiency assay demonstrated a superior therapeutic efficacy of PdCu+Laser group in comparison to the other groups Figure 3i, which is consistent with the above results.…”

Dual enzyme-mimicking carbon dots for enhanced antibacterial activity

“…Besides, it has been demonstrated that Co is capable of deforming the cell membrane structure of bacteria and has the potential to confer enzyme-like activities. 30,31 Co single-atom nanozymes have been confirmed to derive their oxidase-like activity 32 and POD-like activity 33 from the active site of Co–N coordination. Using a transition metal compound as one of the precursors is the most common way of synthesizing nanozymes.…”

Single-atom nanozymes as promising catalysts for biosensing and biomedical applications

“…One can envision that precise drug administration can be achieved when drugs are loaded onto the SAzymes for targeted transport to the cancer sites. 176 In conclusion, targeted tumor therapy has remained a key clinical challenge, and SAzymes have emerged as a unique platform, which demands further and more thorough studies.…”