Nanocatalytic Theranostics with Glutathione Depletion and Enhanced Reactive Oxygen Species Generation for Efficient Cancer Therapy

Advanced Materials, Год журнала: 2021, Номер 33(7)

Опубликована: Янв. 4, 2021

Chemodynamic therapy (CDT) is an emerging method that kills cancer cells by converting intracellular hydrogen peroxide (H2 O2 ) into highly toxic hydroxyl radicals (• OH). To overcome the current limitations of insufficient endogenous H2 and high concentration glutathione (GSH) in tumor cells, intelligent nanocatalytic theranostics (denoted as PGC-DOX) possesses both self-supply GSH-elimination properties for efficient presented. This nanoplatform constructed a facile one-step biomineralization using poly(ethylene glycol)-modified glucose oxidase (GOx) template to form biodegradable copper-doped calcium phosphate nanoparticles, followed loading doxorubicin (DOX). As enzyme catalyst, GOx can effectively catalyze generate , which not only starves but also supplies subsequent Fenton-like reaction. Meanwhile, redox reaction between released Cu2+ ions GSH will induce depletion reduce Fenton agent Cu+ ions, then trigger • OH -mediated reaction, resulting enhanced CDT efficacy. The integration GOx-mediated starvation therapy, CDT, DOX-induced chemotherapy, endow PGC-DOX with effective growth inhibition minimal side effects vivo.

Язык: Английский

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Bioinspired Construction of a Nanozyme-Based H₂O₂ Homeostasis Disruptor for Intensive Chemodynamic Therapy

Journal of the American Chemical Society, Год журнала: 2020, Номер 142(11), С. 5177 - 5183

Опубликована: Фев. 26, 2020

The insufficient intracellular H2O2 level in tumor cells is closely associated with the limited efficacy of chemodynamic therapy (CDT). Despite tremendous efforts, engineering CDT agents a straightforward and secure supplying ability remains great challenge. Inspired by balance generation elimination cancer cells, herein, nanozyme-based homeostasis disruptor fabricated to elevate through facilitating production restraining for enhanced CDT. In formulation, superoxide dismutase-mimicking activity can convert O2•– H2O2, promoting H2O2. Simultaneously, suppression catalase depletion glutathione weaken transformation H2O. Thus, well-defined system could perturb give rise accumulation cells. raised would ultimately amplify Fenton-like reaction-based efficiency. Our work not only paves way engineer alternative intensive but also provides new insights into construction bioinspired materials.

Язык: Английский

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GSH‐Depleted Nanozymes with Hyperthermia‐Enhanced Dual Enzyme‐Mimic Activities for Tumor Nanocatalytic Therapy

Advanced Materials, Год журнала: 2020, Номер 32(42)

Опубликована: Сен. 11, 2020

Abstract Nanocatalytic therapy, using artificial nanoscale enzyme mimics (nanozymes), is an emerging technology for therapeutic treatment of various malignant tumors. However, the relatively deficient catalytic activity nanozymes in tumor microenvironment (TME) restrains their biomedical applications. Here, a versatile and bacteria‐like PEG/Ce‐Bi@DMSN nanozyme developed by coating uniform Bi 2 S 3 nanorods (NRs) with dendritic mesoporous silica (Bi @DMSN) then decorating ultrasmall ceria into large mesopores @DMSN. The exhibit dual enzyme‐mimic activities (peroxidase‐mimic catalase‐mimic) under acidic conditions that can regulate TME, is, simultaneously elevate oxidative stress relieve hypoxia. In addition, effectively consume overexpressed glutathione (GSH) through redox reaction. Photothermal therapy (PTT) introduced to synergistically improve enzyme‐mimicking depletion GSH tumors photonic hyperthermia. This achieved taking advantage desirable light absorbance second near‐infrared (NIR‐II) window nanozymes. Subsequently reactive oxygen species (ROS)‐mediated efficiency significantly improved. Therefore, this study provides proof concept hyperthermia‐augmented multi‐enzymatic ablation.

Язык: Английский

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Piezocatalytic Tumor Therapy by Ultrasound‐Triggered and BaTiO₃‐Mediated Piezoelectricity

Advanced Materials, Год журнала: 2020, Номер 32(29)

Опубликована: Июнь 14, 2020

Abstract Ultrasound theranostics features non‐invasiveness, minor energy attenuation, and high tissue‐penetrating capability, is playing ever‐important roles in the diagnosis therapy of diseases clinics. Herein, ultrasound employed as a microscopic pressure resource to generate reactive oxygen species (ROS) for piezocatalytic tumor under catalytic mediation by piezoelectric tetragonal BaTiO 3 (T‐BTO). Under ultrasonic vibration, electrons holes are unpaired they separated piezoelectricity, resulting establishment strong built‐in electric field, which subsequently catalyzes generation ROS such toxic hydroxyl ( • OH) superoxide radicals O 2 − ) situ eradication. This modality shows intriguing advantages over typical sonoluminescence‐activated sonodynamic therapy, more stable sensitizers dynamical control redox reaction outcomes. Furthermore, according finite element modeling simulation, field capable modulating band alignment make energetically favorable. Both detailed vitro cellular level evaluation vivo xenograft assessment have demonstrated that an injectable T‐BTO‐nanoparticles‐embedded thermosensitive hydrogel will substantially induce irradiation‐triggered cytotoxicity eradication, accompanied therapeutic biosafety vivo.

Язык: Английский

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Metal–Organic Framework Derived Nanozymes in Biomedicine

Accounts of Chemical Research, Год журнала: 2020, Номер 53(7), С. 1389 - 1400

Опубликована: Июнь 29, 2020

ConspectusNanozymes, which integrate the advantages of both nanomaterials and natural enzymes, have accumulated enormous research interest over past decades because opportunity they provide to appreciate further cultivate artificial enzymes with comparable properties. By mimicking coordination environments catalytic sites in nanozymes confined nanostructures can serve as substitutes many processes activity robust stability even harsh conditions. Since pioneering report about peroxidase-mimicking ferromagnetic nanoparticles 2007, been developed specialized for intrinsic enzyme-mimicking property. With rapid development nanoscience nanotechnology, superior advantages, such large-scale production, desired activity, stability, bridge nanozymes.Metal–organic frameworks (MOFs) their derivatives hold great promise direct surrogates conventional enzymatic reactions. According chemical nature, MOF-based be divided into three main categories: pristine MOFs, enzyme-encapsulated MOF composites, derivatives. Due versatility metallic nodes bridging linkers together feasibility postsynthetic engineering modification, MOFs are envisioned one most appropriate this purpose. Using precursors or sacrificial templates, multiple including carbon-based (e.g., heteroatom-doped carbon M–N–C moiety), metal oxide/carbon nanoparticles, metal/carbon rationally synthesized through one-step carbonization/oxidation indirect post-synthesis treatments linker-exchange node-doping). Compared existing nanozymes, open up a new avenue constructing mesoporous nanozymes. In way, properties still maintained, while greatly improved. Account, we highlight some important advances (including moieties (M = single atom), oxide/carbon, metal/carbon, obtained linker exchange doping strategies) activity. We also demonstrate that, integrating physicochemical activities MOF-derived multifunctional platforms biomedical fields antibacterial agents, biosensors, imaging, cancer therapy, environmental protection. Finally, propose future design principles possible approaches deeper understanding mechanisms, thus pointing out directions offer more opportunities enzyme-engineering industry.

Язык: Английский

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The recent progress on metal–organic frameworks for phototherapy

Chemical Society Reviews, Год журнала: 2021, Номер 50(8), С. 5086 - 5125

Опубликована: Янв. 1, 2021

Some infectious or malignant diseases such as cancers are seriously threatening the health of human beings all over world. The commonly used antibiotic therapy cannot effectively treat these within a short time, and also bring about adverse effects drug resistance immune system damage during long-term systemic treatment. Phototherapy is an emerging antibiotic-free strategy to diseases. Upon light irradiation, phototherapeutic agents can generate cytotoxic reactive oxygen species (ROS) induce temperature increase, which leads death targeted cells. These two kinds killing strategies referred photodynamic (PDT) photothermal (PTT), respectively. So far, many photo-responsive have been developed. Among them, metal-organic framework (MOF) becoming one most promising materials because its structure chemical compositions be easily modulated achieve specific functions. MOFs intrinsic ability under rational design MOF construction, serve carrier therapeutic agents, owing tunable porosity. provide feasibility for various combined therapies targeting methods, improves efficiency phototherapy. In this review, we firstly investigated principles phototherapy, comprehensively summarized recent advances in PDT, PTT synergistic therapy, from construction modification. We expect that our demonstration will shed on future development field, it step closer clinical trials.

Язык: Английский

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Self‐Supply of O₂ and H₂O₂ by a Nanocatalytic Medicine to Enhance Combined Chemo/Chemodynamic Therapy

Advanced Science, Год журнала: 2019, Номер 6(24)

Опубликована: Окт. 24, 2019

Combined chemo/chemodynamic therapy is a promising strategy to achieve an improved anticancer effect. However, the hypoxic microenvironment and limited amount of H

Язык: Английский

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Single‐Atom Catalysts in Catalytic Biomedicine

Advanced Materials, Год журнала: 2020, Номер 32(8)

Опубликована: Янв. 13, 2020

The intrinsic deficiencies of nanoparticle-initiated catalysis for biomedical applications promote the fast development alternative versatile theranostic modalities. catalytic performance and selectivity are critical issues that challenging to be augmented optimized in biological conditions. Single-atom catalysts (SACs) featuring atomically dispersed single metal atoms have emerged as one most explored biomedicine recently due their preeminent activity superior distinct from nanosized counterparts. Herein, an overview pivotal significance SACs some underlying need addressed is provided, with a specific focus on applications. Their fabrication strategies, surface engineering, structural characterizations discussed briefly. In particular, triggering representative reactions providing fundamentals use discussed. A sequence paradigms summarized successful construction varied (e.g., cancer treatment, wound disinfection, biosensing, oxidative-stress cytoprotection) emphasis uncovering mechanisms understanding structure–performance relationships. Finally, opportunities challenges faced future SACs-triggered outlooked.

Язык: Английский

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Bioinspired Copper Single‐Atom Catalysts for Tumor Parallel Catalytic Therapy

Advanced Materials, Год журнала: 2020, Номер 32(36)

Опубликована: Июль 23, 2020

Abstract The oxidation of intracellular biomolecules by reactive oxygen species (ROS) forms the basis for ROS‐based tumor therapy. However, current therapeutic modalities cannot catalyze H 2 O and concurrently ROS generation, thereby leading to unsatisfactory efficacy. Herein, it is reported a bioinspired hollow N‐doped carbon sphere doped with single‐atom copper (Cu‐HNCS) that can directly decomposition both hydrogen peroxide ROS, namely superoxide ion (O • − ) hydroxyl radical (•OH), respectively, in an acidic microenvironment without external energy input, thus resulting enhanced growth inhibitory effect. Notably, Fenton reaction turnover frequency Cu Cu‐HNCS ≈5000 times higher than Fe commercial 3 4 nanoparticles. Experimental results density functional theory calculations reveal high catalytic activity originates from copper, calculation predicts next‐generation catalyst. This work provides effective paradigm parallel therapy considerably

Язык: Английский

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A Metal‐Organic Framework (MOF) Fenton Nanoagent‐Enabled Nanocatalytic Cancer Therapy in Synergy with Autophagy Inhibition

Advanced Materials, Год журнала: 2020, Номер 32(12)

Опубликована: Фев. 13, 2020

Nanocatalytic medicine has been developed recently to trigger intratumoral generation of highly toxic reactive oxygen species (ROS) for cancer therapy, which, unfortunately, suffers from compromised therapeutic efficacy due a self-protective mechanism, autophagy, cells mitigate oxidative damage. In this work, during the efforts ROS by nanocatalytic medicine, pharmacological autophagy inhibition strategy is implemented augmenting ROS-induced damage synergetic therapy. An iron-containing metal-organic framework [MOF(Fe)] nanocatalyst as peroxidase mimic used catalyze oxidizing •OH radicals specifically within cells, while chloroquine applied deacidify lysosomes and inhibit cutting off self-protection pathway under severe stress. Cancer fail extract their components detoxicate strengthen themselves, finally succumbing Both in vitro vivo results demonstrate synergy between therapy inhibition, suggesting that such combined applicable amplify tumor-specific may be informative future design regimen.

Язык: Английский

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