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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Conquering the Hypoxia Limitation for Photodynamic Therapy

Advanced Materials, Год журнала: 2021, Номер 33(48)

Опубликована: Сен. 27, 2021

Photodynamic therapy (PDT) has aroused great research interest in recent years owing to its high spatiotemporal selectivity, minimal invasiveness, and low systemic toxicity. However, due the hypoxic nature characteristic of many solid tumors, PDT is frequently limited therapeutic effect. Moreover, consumption O2 during may further aggravate tumor condition, which promotes proliferation, metastasis, invasion resulting poor prognosis treatment. Therefore, numerous efforts have been made increase content with goal enhancing efficacy. Herein, these strategies developed past decade are comprehensively reviewed alleviate hypoxia, including 1) delivering exogenous directly, 2) generating situ, 3) reducing cellular by inhibiting respiration, 4) regulating TME, (e.g., normalizing vasculature or disrupting extracellular matrix), 5) hypoxia-inducible factor 1 (HIF-1) signaling pathway relieve hypoxia. Additionally, -independent Type-I also discussed as an alternative strategy. By reviewing progress, it hoped that this review will provide innovative perspectives new nanomaterials designed combat hypoxia avoid associated limitation PDT.

Язык: Английский

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A Multifunctional Cascade Bioreactor Based on Hollow‐Structured Cu₂MoS₄ for Synergetic Cancer Chemo‐Dynamic Therapy/Starvation Therapy/Phototherapy/Immunotherapy with Remarkably Enhanced Efficacy

Advanced Materials, Год журнала: 2019, Номер 31(51)

Опубликована: Ноя. 4, 2019

The unique tumor microenvironment (TME) facilitates cancer proliferation and metastasis, it is hard to cure completely via monotherapy. Herein, a multifunctional cascade bioreactor based on hollow mesoporous Cu2 MoS4 (CMS) loaded with glucose oxidase (GOx) constructed for synergetic therapy by chemo-dynamic (CDT)/starvation therapy/phototherapy/immunotherapy. CMS harboring multivalent elements (Cu1+/2+ , Mo4+/6+ ) exhibit Fenton-like, glutathione (GSH) peroxidase-like catalase-like activity. Once internalized into the tumor, could generate ·OH CDT Fenton-like reaction deplete overexpressed GSH in TME alleviate antioxidant capability of tumors. Moreover, under hypoxia TME, react endogenous H2 O2 activating catalyzed oxidation GOx starvation accompanied regeneration . regenerated can devote realizing GOx-catalysis-enhanced CDT. Meanwhile, 1064 nm laser irradiation shows remarkable tumor-killing ability phototherapy due its excellent photothermal conversion efficiency (η = 63.3%) cytotoxic superoxide anion (·O2- generation performance. More importantly, PEGylated CMS@GOx-based synergistic combined checkpoint blockade elicit robust immune responses both effectively ablating primary tumors inhibiting metastasis.

Язык: Английский

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Manganese Oxide Nanomaterials: Synthesis, Properties, and Theranostic Applications

Advanced Materials, Год журнала: 2020, Номер 32(10)

Опубликована: Янв. 28, 2020

Abstract Despite the comprehensive applications in bioimaging, biosensing, drug/gene delivery, and tumor therapy of manganese oxide nanomaterials (MONs including MnO 2 , MnO, Mn O 3 4 x ) their derivatives, a review article focusing on MON‐based nanoplatforms has not been reported yet. Herein, representative progresses MONs synthesis, heterogene, properties, surface modification, toxicity, imaging, biodetection, are mainly introduced. First, five kinds primary synthetic methods presented, thermal decomposition method, exfoliation strategy, permanganates reduction adsorption–oxidation hydro/solvothermal. Second, preparations hollow composite materials summarized specially. Then, chemical toxicity discussed. Next, diagnostic imaging sensing outlined. Finally, some rational designs photodynamic therapy, photothermal chemodynamic sonodynamic radiotherapy, magnetic hyperthermia, chemotherapy, gene starvation ferroptosis, immunotherapy, various combination highlighted.

Язык: Английский

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Biodegradable Manganese-Doped Calcium Phosphate Nanotheranostics for Traceable Cascade Reaction-Enhanced Anti-Tumor Therapy

ACS Nano, Год журнала: 2019, Номер 13(12), С. 13985 - 13994

Опубликована: Дек. 13, 2019

Glucose oxidase (GOx) has been recognized as a "star" enzyme catalyst involved in cancer treatment the past few years. Herein, GOx is mineralized with manganese-doped calcium phosphate (MnCaP) to form spherical nanoparticles (GOx-MnCaP NPs) by an situ biomimetic mineralization method, followed loading of doxorubicin (DOX) construct biodegradable, biocompatible, and tumor acidity-responsive nanotheranostics for magnetic resonance imaging (MRI) cascade reaction-enhanced cooperative treatment. The GOx-driven oxidation reaction can effectively eliminate intratumoral glucose starvation therapy, elevated H2O2 then converted into highly toxic hydroxyl radicals via Mn2+-mediated Fenton-like chemodynamic therapy (CDT). Moreover, acidity amplification due gluconic acid generation will turn accelerate degradation nanoplatform promote Mn2+-H2O2 enhanced CDT. Meanwhile, released Mn2+ ions be used MRI monitor process. After carrying anticancer drug, DOX-loaded GOx-MnCaP integrate CDT, DOX-induced chemotherapy together, which showed greatly improved therapeutic efficacy than each monotherapy. Such orchestrated demonstrated high-efficiency suppression on 4T1 tumor-bearing mice minimal side effects. Our findings suggested that excellent biodegradability biocompatibility hold clinical translation potential management.

Язык: Английский

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Recent Advances in Hyperthermia Therapy‐Based Synergistic Immunotherapy

Advanced Materials, Год журнала: 2020, Номер 33(4)

Опубликована: Дек. 2, 2020

Abstract The past decades have witnessed hyperthermia therapy (HTT) as an emerging strategy against malignant tumors. Nanomaterial‐based photothermal (PTT) and magnetic (MHT), highly effective noninvasive treatment models, offer advantages over other strategies in the of different types However, both PTT MHT cannot completely cure cancer due to recurrence distal metastasis. In recent years, immunotherapy has attracted widespread attention owing its capability activate body's own natural defense identify, attack, eradicate cells. Significant efforts been devoted studying activated immune responses caused by hyperthermia‐ablated this article, synergistic mechanism HTT immunotherapy, including immunogenic cell death reversal immunosuppressive tumor microenvironment is discussed. reports combination or HTT‐based multimodal with immunoadjuvant exploitation, checkpoint blockade therapy, adoptive cellular are summarized. As highlighted, these could achieve synergistically enhanced therapeutic outcomes primary tumors metastatic lesions, prevent recurrence, prolong survival period. Finally, current challenges prospective developments HTT‐synergized also reviewed.

Язык: Английский

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Manipulating Intratumoral Fenton Chemistry for Enhanced Chemodynamic and Chemodynamic‐Synergized Multimodal Therapy

Advanced Materials, Год журнала: 2021, Номер 33(48)

Опубликована: Сен. 27, 2021

Chemodynamic therapy (CDT) uses the tumor microenvironment-assisted intratumoral Fenton reaction for generating highly toxic hydroxyl free radicals (•OH) to achieve selective treatment. However, limited efficiency restricts therapeutic efficacy of CDT. Recent years have witnessed impressive development various strategies increase reaction. The introduction these reinforcement can dramatically improve treatment CDT and further promote enhanced (ECDT)-based multimodal anticancer treatments. In this review, authors systematically introduce strategies, from their basic working principles, mechanisms representative clinical applications. Then, ECDT-based is discussed, including how integrate emerging accelerating therapy, as well synergistic ECDT other methods. Eventually, future direction challenges therapies are elaborated, highlighting key scientific problems unsolved technical bottlenecks facilitate translation.

Язык: Английский

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Recent Advances in Nanomaterial‐Based Nanoplatforms for Chemodynamic Cancer Therapy

Advanced Functional Materials, Год журнала: 2021, Номер 31(22)

Опубликована: Март 8, 2021

Abstract Triggered by the endogenous chemical energy in tumor microenvironment (TME), chemodynamic therapy (CDT) as an emerging non‐exogenous stimulant therapeutic modality has received increasing attention recent years. The agents can convert internal hydrogen peroxide (H 2 O ) into lethal reactive oxygen species (ROS) hydroxyl radicals ( • OH) for oncotherapy. Compared with other modalities, CDT possesses many notable advantages, such tumor‐specific, highly selective, fewer systemic side effects, and no need external stimulation. Nevertheless, mild acid pH, low H content, overexpressed reducing substance TME severely suppressed efficiency. With rapid development of nanotechnology, some kinds nanomaterials have been utilized improved In particular, excellent photo‐, ultrasound‐, magnetic‐, stimuli‐response properties make it possible combination cancer shown superior anti‐cancer activity than monotherapies. Therefore, is necessary to summarize application nanomaterial‐based therapy. this review, various nanomaterials‐based nanoplatforms its combinational therapies are summarized discussed, aiming provide inspiration design better‐quality promote lay foundation future conversion clinical applications.

Язык: Английский

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Nanozymes-Engineered Metal–Organic Frameworks for Catalytic Cascades-Enhanced Synergistic Cancer Therapy

Nano Letters, Год журнала: 2019, Номер 19(8), С. 5674 - 5682

Опубликована: Июль 30, 2019

The efficiency of chemical intercommunication between enzymes in natural networks can be significantly enhanced by the organized catalytic cascades. Nevertheless, exploration two-or-more-enzymes-engineered nanoreactors for cascades remains a great challenge cancer therapy because inherent drawbacks enzymes. Here, encouraged activity individual nanozyme benefiting treatment solid tumors, we propose an situ cascades-enhanced synergistic therapeutic strategy driven dual-nanozymes-engineered porphyrin metal–organic frameworks (PCN). Precisely, catalase-mimicking platinum nanoparticles (Pt NPs) were sandwiched PCN, followed embedding glucose oxidase-mimicking ultrasmall gold (Au within outer shell, and further coordination with folic acid (P@Pt@P–Au–FA). Pt NPs effectively enabled tumor hypoxia relief catalyzing intratumoral H2O2 to O2 (1) enhancing O2-dependent photodynamic (2) subsequently accelerating depletion β-d-glucose Au starving-like self-produced as substrate NPs. Consequently, remarkably strengthened antitumor prevention recurrence metastasis was achieved. This work highlights rationally designed microenvironment-specific nanoreactor opening improved research nanozymes provides means design cascade model practical applications.

Язык: Английский

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Glutathione-Depleting Nanomedicines for Synergistic Cancer Therapy

ACS Nano, Год журнала: 2021, Номер 15(5), С. 8039 - 8068

Опубликована: Май 11, 2021

Cancer cells frequently exhibit resistance to various molecular and nanoscale drugs, which inevitably affects the drugs' therapeutic outcomes. Overexpression of glutathione (GSH) has been observed in many cancer cells, solid evidence corroborated resulting tumor a variety anticancer therapies, suggesting that this biochemical characteristic can be developed as potential target for treatments. The single treatment GSH-depleting agents potentiate responses different cell death stimuli; therefore, an adjunctive strategy, GSH depletion is usually combined with mainstream therapies enhancing Propelled by rapid development nanotechnology, readily constructed into nanomedicines, have shown steep rise over past decade. Here, we review common nanomedicines widely applied synergistic treatments recent years. Some current challenges future perspectives depletion-based are also presented. With understanding structure–property relationship action mechanisms these biomaterials, hope nanotechnology will further realize more effective disease even achieve successful clinical translations.

Язык: Английский

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