Nanocarbon Framework-Supported Ultrafine Mo₂C@MoO_x Nanoclusters for Photothermal-Enhanced Tumor-Specific Tandem Catalysis Therapy

Abstract

Recent advances in the synthesis of multifunctional nanomaterials create new opportunities for the rational design of multimodal chemodynamic therapy (CDT) agents. Precisely tailoring the nanostructure and composition of CDT nanoagents for maximum efficacy remains a challenge. Herein, we report the successful synthesis of nanocarbon framework-supported ultrafine Mo2C@MoO x nanoclusters (C/Mo2C@MoO x ) via a pyrolysis of a Mo/ZIF-8 MOF precursor at 900 °C followed by mild surface oxidation. The developed C/Mo2C@MoO x composite demonstrated outstanding performance in photothermal-enhanced tumor-specific tandem catalysis therapy. Specifically, C/Mo2C@MoO x efficiently catalyzed the conversion of endogenous H2O2 to cytotoxic 1O2 via a Russell mechanism, while also converting the O2 byproduct to cytotoxic ·O2 – via an oxidase-like mechanism. A high dispersion of active Mo5+ sites in the exposed MoO x shell enhanced the reactive oxygen species (ROS)-generating efficiency of C/Mo2C@MoO x . Moreover, the Mo2C core in the ultrafine Mo2C@MoO x nanoclusters allowed NIR-II (1064 nm)-driven photothermal heating, which significantly boosted the CDT process through photothermal effects. Additionally, the CDT process relied on a redox cycle involving Mo5+/Mo6+ species, which could be sustained by glutathione (GSH) consumption. Given these advantages, C/Mo2C@MoO x demonstrated remarkable synergistic therapeutic efficacy for cancer treatment (both in vitro and in vivo) through tumor microenvironment-stimulated generation of multiple ROS and NIR-II photothermal activity.

Prospects of nano-carbons as emerging catalysts for enzyme-mimetic applications

“…The catalytic mechanism involves absorption of NIR light, generation of cytotoxic heat, and the regulation of ROS generation activity. 169 Sun et al investigated the underlying mechanism of peroxidase-like activity and protective effect of GOQDs toward the acceleration of alcohol metabolism and treatment of alcoholic liver disease. GOQDs were found to decrease mitochondrial damage and ROS generation.…”

Vacancy defect-promoted nanomaterials for efficient phototherapy and phototherapy-based multimodal Synergistic Therapy

“…It is worth noting that various nanomaterials have made significant contributions to phototherapy through both improving targeted therapeutic efficiency and reducing side effects ( Cheng et al, 2014 ; Liu Y. et al, 2019 ; Liu et al, 2021 ). Nanomaterials for phototherapy are usually composed of inorganic nanoparticles with strong NIR absorption and rapid NIR activation, such as noble metal, chalcogenide, transition metal oxide, polyoxometalate, transition metal carbide, and carbon-based nanoparticles ( Wang X. et al, 2019 ; Liu G. et al, 2019 ; Gu et al, 2019 ; Wang L. et al, 2020 ; Wang L. et al, 2021 ; Tian et al, 2021 ). The most key factor affecting the performance of phototherapeutic nanomaterials is their microstructure (i.e., electronic and geometric structures) which in principle determines their physicochemical properties and the resulting phototherapeutic efficacy ( Coughlan et al, 2017 ; Huang et al, 2017 ; Nosaka and Nosaka, 2017 ; Chen et al, 2021 ; Liu et al, 2021 ).…”

“… Schematic Illustration of the synthesis of CoFe-500 for PA/MR/NIR imaging-guided PTT, Fourier-transform EXAFS spectra at Co K-edge for various CoFe-x samples, Co 2p XPS spectra for CoFe-500 and CoFe-800, Co 2+ defect/Co 2+ peak area ratio for various CoFe-x samples, and optimized geometries for a CoFe-500 bulk heterojunction composed of CoO-V Co and CoFe 2 O 4 -V Co , band structures of CoO-V Co and CoFe 2 O 4 -V Co , 3D PAI images of tumor site at 6 h postinjection, in vivo T1-MRI imaging of HeLa-bearing mice before and after injected with CoFe-500, and photographs at different times after various treatments. Reproduced with permission from Wang L. et al (2021) . Copyright © 2020 American Chemical Society.…”

“…In addition to transition metal nanocompounds, carbon-based nanomaterials, including but not limited to graphene, carbon quantum dots, and derivatives of metal−organic frameworks (MOFs), are also promising candidates as nanomaterials for phototherapy ( Lu L. et al, 2018 ; Chen et al, 2021 ; Tamtaji et al, 2021 ; Tian et al, 2021 ). Meanwhile, carbon vacancy defects in carbon-based nanomaterials can significantly influence their configuration and atomic arrangements and effectively regulate the local π-electron system, so as to tailor the global properties of phototherapeutic nanomaterials and to achieve desired phototherapy effects ( Liang et al, 2015 ; Li et al, 2017 ; Liu H. et al, 2020 ; Weng et al, 2020 ; Wang L. et al, 2021 ; Chang et al, 2021 ; Chen et al, 2021 ; Guo et al, 2021 ; Tamtaji et al, 2021 ). Guan et al ( Weng et al, 2020 ) reported that a series of vacancy defective nanocarbon polyhedral-supported Cu nanoparticles (Cu@CPP- t , t represented different calcination temperatures) as novel photothermal agents were successfully prepared through the controlled calcination of Cu-based MOF (Cu-BTC) precursors at temperatures from 400 to 900°C Specifically, Cu@CPP- t samples comprised partially oxidized Cu nanoparticles dispersed on nanocarbon polyhedra, and their nanocarbon supports were semigraphitic phase with abundant carbon vacancies.…”

“…4) In addition, it should also show low toxicity but high biocompatibility to realize minimized side effects. Recently, thus, a great deal of efforts have been made to develop novel phototherapeutic nanomaterials with well-defined particle sizes, morphology, and compositions, such as various noble metal, semiconductor, and carbon-based nanomaterials ( Gao et al, 2018 ; Gu et al, 2019 ; Melo-Diogo et al, 2019 ; Wang L. et al, 2020 ; Zhou et al, 2020 ; Chang et al, 2021 ; Tian et al, 2021 ; Wang L. et al, 2021 ; Zhou C. et al, 2021 ). So far, however, the rational design and controllable synthesis of phototherapeutic nanomaterials in order to satisfy the above four properties simultaneously remains a vitally important and fundamental scientific problem.…”