A Unique Multifunctional Nanoenzyme Tailored for Triggering Tumor Microenvironment Activated NIR‐II Photoacoustic Imaging and Chemodynamic/Photothermal Combined Therapy

Abstract

The accurate diagnosis and targeted therapy of malignant tumors face significant challenges. To address these, an oxidized molybdenum polyoxometalate-copper nanocomposite (Ox-POM@Cu) is designed and synthesized here. The doping with Cu determines the formation of oxygen vacancies, which can increase the carrier concentration in Ox-POM@Cu, accelerate electron transfer, and enhance the redox activity, thus playing an efficient catalytic role. The nanocomposite presents unique enzymatic functions characterized by a multielement catalytic activity in the tumor microenvironment (TME). In addition, it can be employed as an NIR-II photoacoustic imaging (PAI) probe and cancer therapy agent. First, it participates in a redox reaction with glutathione (GSH) in tumor tissues, activates the PAI and photothermal therapy functions via NIR-II irradiation, and depletes the GSH supply in cancerous cells. Subsequently, it catalyzes a Fenton-like reaction with H 2 O 2 in tumor tissues to form hydroxyl radicals, thereby performing a chemodynamic therapy function. The findings show that the developed nanoenzyme is very efficient in the diagnosis and treatment of malignant tumors. This work not only provides a new strategy for the design of TME-induced NIR-II PAI but also presents new insights into enhanced cancer therapy.

MOF-coated upconversion nanoconstructs for synergetic photo-chemodynamic/oxygen-elevated photodynamic therapy

“…On the other hand, Cu 2+ doping increases the formation of oxygen vacancies, accelerates the electron transfer of MIL-100(Fe) and enhances the redox activity, thus accelerating the reduction of Fe 3+ to Fe 2+ , and thereby can produce more ˙OH and play an effective catalytic role (eqn (8)). 47,48…”

“…On the other hand, Cu 2+ doping increases the formation of oxygen vacancies, accelerates the electron transfer of MIL-100(Fe) and enhances the redox activity, thus accelerating the reduction of Fe 3+ to Fe 2+ , and thereby can produce more • OH and play an effective catalytic role (eqn (8)). 47,48 In consideration of the relatively weak red UCL of UC that might be not enough to trigger efficient PDT of Ce6, a 671 nm laser (15 mW cm −2 ) was introduced to evaluate the PDT capacity of UCTSCF. 1 O 2 is able to react with DPBF and induce obvious DPBF fading.…”

Acoustic-Based Theranostic Probes Activated by Tumor Microenvironment for Accurate Tumor Diagnosis and Assisted Tumor Therapy

“…Moreover, in the presence of reductive TME, there was a significant enhancement in the NIR absorption of SPB@POM, leading to a further improvement in the PAI contrast and PTT efficacy. Similarly, Wang et al developed an oxidized molybdenum polyoxometalate-copper nanocomposite (Ox-POM@Cu) as a multifunctional nanozyme that displayed glutathione peroxidase (GSH-PX) and catalase (CAT) activities . Under the trigger of endogenous GSH, the doped Mo 6+ and Cu 2+ in Ox-POM@Cu would be reduced into Mo 5+ and Cu + , respectively, and simultaneously activate the absorbance of POM in the NIR-II section for responsive PAI and PTT.…”

“…Similarly, Wang et al developed an oxidized molybdenum polyoxometalatecopper nanocomposite (Ox-POM@Cu) as a multifunctional nanozyme that displayed glutathione peroxidase (GSH-PX) and catalase (CAT) activities. 182 Under the trigger of endogenous GSH, the doped Mo 6+ and Cu 2+ in Ox-POM@ Cu would be reduced into Mo 5+ and Cu + , respectively, and simultaneously activate the absorbance of POM in the NIR-II section for responsive PAI and PTT. Moreover, the obtained Cu + could occur in a Fenton-like reaction with H 2 O 2 with a fast reaction rate to produce hydroxyl radical (•OH) and achieve CDT.…”

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

“…Although CDT is effective in preventing tumor growth and metastasis, it doesn’t have the ability to completely eliminate the tumor because of insufficient endogenous H 2 O 2 ( Liu Y. et al, 2020 ; Ji S. et al, 2021 ). Thus, oxygen vacancy-promoted synergistic PTT/CDT or PTT/PDT/CDT have been explored to achieve the satisfactory anticancer efficacy, so as to effectively eliminate tumor and inhibit tumor recurrence ( Ji et al, 2019 ; Peng et al, 2020 ; Sun et al, 2020 ; Ji X. et al, 2021 ; Kong et al, 2021 ; Zhang et al, 2021 ; Wang et al, 2022 ; Zhou et al, 2022 ). For instance, Tan et al ( Zhou et al, 2022 ) reported the dark-blue co-intercalated MoO 3− x (denoted as NH−MoO 3− x ) nanobelts via the ball-milling process and then aqueous Na + /H 2 O co-intercalation as efficient nanozymes for photothermal-enhanced CDT.…”