Singlet Oxygen Generation in Dark‐Hypoxia by Catalytic Microenvironment‐Tailored Nanoreactors for NIR‐II Fluorescence‐Monitored Chemodynamic Therapy

Abstract

Singlet oxygen (1O2) has a potent anticancer effect, but photosensitized generation of 1O2 is inhibited by tumor hypoxia and limited light penetration depth. Despite the potential of chemodynamic therapy (CDT) to circumvent these issues by exploration of 1O2‐producing catalysts, engineering efficient CDT agents is still a formidable challenge since most catalysts require specific pH to function and become inactivated upon chelation by glutathione (GSH). Herein, we present a catalytic microenvironment‐tailored nanoreactor (CMTN), constructed by encapsulating MoO42− catalyst and alkaline sodium carbonate within liposomes, which offers a favorable pH condition for MoO42−‐catalyzed generation of 1O2 from H2O2 and protects MoO42− from GSH chelation owing to the impermeability of liposomal lipid membrane to ions and GSH. H2O2 and 1O2 can freely cross the liposomal membrane, allowing CMTN with a built‐in NIR‐II ratiometric fluorescent 1O2 sensor to achieve monitored tumor CDT.

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 overcome the deficiency of nanozyme which warranted specific pH to maintain activity and became inactivated by GSH chelation, Chen et al [59] presented a catalytic microenvironment-tailored nanoreactors (CMTN), formulated by surface conjugation of MoO 4 2À catalyst and alkaline sodium carbonate (ACS). MoO 4 2À exhibited superior catalytic performance to yield 1 O 2 from H 2 O 2 at pH 10.0-11.0.…”

“…Reproduced with permission. [59] Copyright 2021, Wiley-VCH. D,E) Schematic illustration of the synthesis of HSC-2 and adjustable PA/fluorescence imaging-guided PTT/catalytic therapy in NIR-II window.…”

“…B) In vivo NIR-II fluorescence images of MCF-7 tumor-bearing mice after intravenous injection with CMTNs@IR1061/DCNPs or C) liposomes@IR1061/DCNPs. Reproduced with permission [59]. Copyright 2021, Wiley-VCH.…”

PDGFB targeting biodegradable FePt alloy assembly for MRI guided starvation-enhancing chemodynamic therapy of cancer

“…However, UION-based CDT is still incapable of inducing cancer cell death. This is mainly due to the following two reasons: (1) Fenton catalytic efficacy of UION is only effective under highly acidic conditions [ 21 ]. In weakly acidic TME, the CDT induced by the UION-mediated Fenton reaction is relatively inefficient and insufficient to effectively inhibit tumor growth [ 22 , 23 ].…”