A Titanium Nitride Nanozyme for pH‐Responsive and Irradiation‐Enhanced Cascade‐Catalytic Tumor Therapy

Abstract

Nanozyme-based catalytic tumor therapyi sa n emerging therapeutic method with high reactivity in response to tumor microenvironments (TMEs). To overcome the current limitations of deficient catalytic activity of nanozymes,w e studied the contributing factors of enzymatic activity based on non-metallic-atom doping and irradiation. Nitrogen doping significantly enhanced the peroxidase activity of Ti-based nanozymes,whichwas shown experimentally and theoretically. Based on the excellent NIR-adsorption-induced surface plasmon resonance and photothermal effect, the enzymatic activity of TiNn anoparticles (NPs) was further improved under NIR laser irradiation. Hence,a na cidic TME-responsive and irradiation-mediated cascade nanocatalyst (TLGp) is presented by using TiN-NP-encapsulated liposomes linked with pHresponsive PEG-modified glucose oxidase (GOx). The integration of pH-responsive GOx-mediated H 2 O 2 self-supply, nitrogen-doping,a nd irradiation-enhanced enzymatic activity of TiNN Ps and mild-photothermal therapye nables an effective tumor inhibition by TLGp with minimal side effects in vivo.

Nanobiomimetic Medicine

“…of Cu. [145] Analogously, Mn-based [146] and Ti-based [147] nanosystems also confirmed the pivotal role of POD enzymes in tumor therapy.…”

Novel Strategy for Optimized Nanocatalytic Tumor Therapy: From an Updated View

“…As such, the in-depth studies of the molecular mechanism of NCT combating tumor cells should also be highlighted, which would promote the development of NCT on pharmacological research, targeted therapy, and further clinical application. 3) Third, the process of Catalytic reaction Nanozyme Fe, Cu, Mn, Ce, MOF-based nanocomposites [11] Surface modification [24] Morphological (2D) nanozyme [26] SACs [29] TME modulating Co-loaded catalysts to promote sequential catalytic reactions [32b,34] Self-amplified H 2 O 2 level [35,36] Improving the GSH/pH condition [37,40] Construction of multifunctional nanosystems Synergistic therapy NCTþchemotherapy [13] NCTþstimuli-responsive therapy [45][46][47][48] NCT þ PDT/ PTT [44] NCTþgene-editing therapy [50] NCTþimmumotherapy [53,57] Targeted therapy / Vehicle mediated [41] Surface ligand mediated [43] Theranostic applications / Fluorescence imaging-guided NCT [59] PA-guided NCT [61] Multimodal imaging-monitored NCT [60] a)…”

“…To explore the impact of PTT effect on NCT, Liu et al [ 45 ] investigated the contributing factors of catalytic performance by surface engineering of nonmetallic atom doping and laser irradiation ( Figure A,B ) . As the experiment indicated, POD reactivity of the Ti‐based nanozyme was significantly enhanced via nitrogen doping (TiN).…”

“…In addition, owing to the excellent PTT effect of TiN induced by near-infrared (NIR) adsorption, its enzymatic performance could be further improved by laser irradiation (Figure 6C). As a result, they successfully synthesized a TME-and laser-responsive nanozyme: TiN-coated liposomes [45] Copyright 2021, Wiley-VCH.…”

“…C) The factors affecting the POD activity of Ti-based nanozymes and pH-responsive/mild PTT-mediated cascade NCT of TLGp nanosystem. Reproduced with permission [45]. Copyright 2021, Wiley-VCH.…”