Two-Dimensional MXene-Originated In Situ Nanosonosensitizer Generation for Augmented and Synergistic Sonodynamic Tumor Nanotherapy

Abstract

Despite the merits of high tissue-penetrating depth, no ionizing radiation, and low cost, sonodynamic therapy (SDT) still suffers from a low quantum yield of reactive oxygen species (ROS), limited delivery efficiency, and potential toxicity of sonosensitizers. Different from the direct delivery of sonosensitizers into tumor tissue for SDT, this work reports the fabrication of two-dimensional (2D) nanosonosensitizers/nanocatalysts (Ti3C2/CuO2@BSA) for the in situ generation of nanosonosensitizers by responding to the tumor microenvironment, achieving the high-performance and synergistic sonodynamic/chemodynamic tumor therapy. CuO2 nanoparticle integration on 2D Ti3C2 MXene achieved in situ H2O2 generation in an acidic tumor microenvironment for oxidizing Ti3C2 to produce TiO2 nanosonosensitizers, accompanied by the enhanced separation of electrons (e–) and holes (h+) by the carbon matrix after oxidation, further augmenting the SDT efficacy. Ultrasound irradiation during the sonodynamic process also enhanced the Cu-initiated Fenton-like reaction to produce more ROS for synergizing the sonodynamic tumor therapy. The experimental results confirm and demonstrate the synergistic therapeutic effects of chemodynamic and sonodynamic nanotherapy both in vitro and in vivo. The antitumor mechanisms of synergistic chemodynamic and sonodynamic therapies are associated with the upregulation of oxidative phosphorylation, ROS generation, and apoptosis as demonstrated by RNA sequencing. This work thus provides a distinct paradigm of 2D MXene-originated in situ nanosonosensitizer generation for augmented and synergistic sonodynamic tumor nanotherapy.

Facile preparation of Ti3C2Tx sheets by selectively etching in a H2SO4/H2O2 mixture

“…More importantly, the layered structure of the obtained Ti 3 C 2 T x sheets is notably different from that of the Ti 3 AlC 2 powders ( Figures 2B–D ), as clearly demonstrated in Figures 3B–D . Particularly, the structure of the obtained Ti 3 C 2 T x sheets has some layered changes, and the lamellae have many hole defects, compared with that of the Ti 3 AlC 2 powders; it is reasoned that when Al layers are etched away, a small amount of Ti layers is also etched out to leave holes and TiO 2 nanoparticles on the surfaces due to the Ti vacancies triggering the oxidation process from Ti to TiO 2 , consistent with the results previous literature reported ( Shi et al, 2022b ; Huang et al, 2022 ; Jiang et al, 2022 ; Ma et al, 2022 ; Zhang et al, 2022 ).…”

Nanosystems for chemodynamic based combination therapy: Strategies and recent advances

“…In addition, ultrasound also enhances the Cu-induced Fenton-like reaction during the sonodynamic process to generate more ROS to achieve sonodynamic/chemodynamic improved synergistic tumor therapy. This study also confirmed that the antitumor mechanism of synergistic chemodynamic and sonodynamic therapies are associated with the upregulation of oxidative phosphorylation and ROS generation ( Zhang M. et al, 2022 ).…”

3-Bromopyruvate-Loaded Ti3C2 MXene/Cu2O Nanosheets for Photoacoustic Imaging-Guided and Hypoxia-Relieving Enhanced Photothermal/Chemodynamic Therapy

“…Ti 3 C 2 MXenes exhibit strong near-infrared (NIR) absorption in the NIR region, which is beneficial for realizing PAI-guided PTT, providing an opportunity for the integration of diagnosis and treatment . It has been reported by Zhang et al that 2D Ti 3 C 2 MXenes/CuO 2 @BSA composite nanosheets can be successfully used in synergistic CDT/SDT . Consequently, it is imperative to focus on the construction of a Ti 3 C 2 MXene/Cu 2 O-based 2D nanoplatform for the practical application of CDT/PTT synchronous multimodal therapy with PAI-guided accurate diagnosis.…”

“…al. that 2D Ti 3 C 2 MXenes/ CuO 2 @BSA composite nanosheets can be successfully used in synergistic CDT/SDT 12. Consequently, it is imperative to focus on the construction of a Ti 3 C 2 MXene/Cu 2 O-based 2D nanoplatform for the practical application of CDT/PTT synchronous multimodal therapy with PAI-guided accurate diagnosis.…”