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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A Tumor‐Microenvironment‐Activated Nanozyme‐Mediated Theranostic Nanoreactor for Imaging‐Guided Combined Tumor Therapy

Advanced Materials, Год журнала: 2019, Номер 31(40)

Опубликована: Авг. 18, 2019

Activatable theranostic agents that can be activated by tumor microenvironment possess higher specificity and sensitivity. Here, activatable nanozyme-mediated 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) loaded ABTS@MIL-100/poly(vinylpyrrolidine) (AMP) nanoreactors (NRs) are developed for imaging-guided combined therapy. The as-constructed AMP NRs specifically the through a "two-step rocket-launching-like" process to turn on its photoacoustic imaging signal photothermal therapy (PTT) function. In addition, simultaneously producing hydroxyl radicals in response high H2 O2 level of disrupting intracellular glutathione (GSH) endows with ability enhanced chemodynamic (ECDT), thereby leading more efficient therapeutic outcome combination tumor-triggered PTT. More importantly, -activated acid-enhanced properties enable specific tumors, leaving normal tissues unharmed. These remarkable features may open new avenue explore nanozyme-involved intelligent, accurate, noninvasive cancer theranostics.

Язык: Английский

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An Enzyme‐Engineered Nonporous Copper(I) Coordination Polymer Nanoplatform for Cuproptosis‐Based Synergistic Cancer Therapy

Advanced Materials, Год журнала: 2022, Номер 34(43)

Опубликована: Сен. 2, 2022

Abstract Cuproptosis, a newly identified form of regulated cell death that is copper‐dependent, offers great opportunities for exploring the use copper‐based nanomaterials inducing cuproptosis cancer treatment. Here, glucose oxidase (GOx)‐engineered nonporous copper(I) 1,2,4‐triazolate ([Cu(tz)]) coordination polymer (CP) nanoplatform, denoted as GOx@[Cu(tz)], starvation‐augmented and photodynamic synergistic therapy developed. Importantly, catalytic activity GOx shielded in scaffold but can be “turned on” efficient depletion only upon glutathione (GSH) stimulation cells, thereby proceeding starvation therapy. The GSH sensitizes cells to GOx@[Cu(tz)]‐mediated cuproptosis, producing aggregation lipoylated mitochondrial proteins, target copper‐induced toxicity. increased intracellular hydrogen peroxide (H 2 O ) levels, due oxidation glucose, activates type I (PDT) efficacy GOx@[Cu(tz)]. vivo experimental results indicate GOx@[Cu(tz)] produces negligible systemic toxicity inhibits tumor growth by 92.4% athymic mice bearing 5637 bladder tumors. This thought first report cupreous nanomaterial capable cuproptosis‐based cancer, which should invigorate studies pursuing rational design efficacious strategies based on cuproptosis.

Язык: Английский

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Multivariate Modulation of the Zr MOF UiO‐66 for Defect‐Controlled Combination Anticancer Drug Delivery

Angewandte Chemie International Edition, Год журнала: 2020, Номер 59(13), С. 5211 - 5217

Опубликована: Янв. 17, 2020

Metal-organic frameworks (MOFs) are emerging as leading candidates for nanoscale drug delivery, a consequence of their high capacities, ease functionality, and the ability to carefully engineer key physical properties. Despite many anticancer treatment regimens consisting cocktail different drugs, examples delivery multiple drugs from one MOF rare, potentially hampered by difficulties in postsynthetic loading more than cargo molecule. Herein, we report new strategy, multivariate modulation, which allows incorporation up three Zr UiO-66 defect-loading. The added one-pot solvothermal synthesis distributed throughout at defect sites coordination metal clusters. This tight binding comes with retention crystallinity porosity, allowing fourth be postsynthetically loaded into MOFs yield nanoparticles cocktails that show enhancements selective cytotoxicity against MCF-7 breast cancer cells vitro. We believe modulation is significant advance application biomedicine, anticipate protocol will also adopted other areas chemistry, easily produce defective arrays highly functionalised pores potential gas separations catalysis.

Язык: Английский

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Biomimetic Nanotherapies: Red Blood Cell Based Core–Shell Structured Nanocomplexes for Atherosclerosis Management

Advanced Science, Год журнала: 2019, Номер 6(12)

Опубликована: Апрель 24, 2019

Cardiovascular disease is the leading cause of mortality worldwide. Atherosclerosis, one most common forms disease, characterized by a gradual formation atherosclerotic plaque, hardening, and narrowing arteries. Nanomaterials can serve as powerful delivery platforms for atherosclerosis treatment. However, their therapeutic efficacy substantially limited in vivo due to nonspecific clearance mononuclear phagocytic system. In order address this limitation, rapamycin (RAP)-loaded poly(lactic-

Язык: Английский

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Modulating the Biofunctionality of Metal–Organic‐Framework‐Encapsulated Enzymes through Controllable Embedding Patterns

Angewandte Chemie International Edition, Год журнала: 2019, Номер 59(7), С. 2867 - 2874

Опубликована: Ноя. 21, 2019

Abstract Embedding an enzyme within a MOF as exoskeleton (enzyme@MOF) offers new opportunities to improve the inherent fragile nature of enzyme, but also impart novel biofunctionality MOF. Despite remarkable stability achieved for MOF‐embedded enzymes, embedding patterns and conversion enzymatic after entrapment by have only received limited attention. Herein, we reveal how affect bioactivity encapsulated in ZIF‐8. The enzyme@MOF can maintain high activity when encapsulation process is driven rapid enzyme‐triggered nucleation When slow coprecipitation enzymes are not involved ZIF‐8, tends be inactive owing unfolding competing coordination caused ligand, 2‐methyl imidazole. These two easily controlled chemical modification amino acids modulating their biofunctionality.

Язык: Английский

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Tumor-Targeted Cascade Nanoreactor Based on Metal–Organic Frameworks for Synergistic Ferroptosis–Starvation Anticancer Therapy

ACS Nano, Год журнала: 2020, Номер 14(9), С. 11017 - 11028

Опубликована: Авг. 13, 2020

Although ferroptosis therapy has been proven to be a promising strategy for cancer treatment, its efficacy still might limited by insufficient H2O2 supply in tumor tissue. Herein, we designed cell membrane-cloaked cascade nanoreactor based on ferric metal–organic frameworks (MOF) and glucose oxidase (GOx) decoration synergistic ferroptosis–starvation anticancer therapy. The GOx can catalyze generate sufficient therapy, the consumption caused utilized as another attractive treatment called starvation When reached sites, high concentration of GSH reduced Fe3+ trigger structure collapse MOF release Fe2+ catalyzed oxidation H2O2. Then Fenton reaction happened between produce hydroxyl radicals (•OH) promoted With these reactions, was realized. Furthermore, membrane endows homologous targeting immune escaping ability, which facilitated accumulate into site with efficiency. exhibits efficiency suppression situ consumed produced compounds, promote development precise cooperative spatiotemporal controllability.

Язык: Английский

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Cell membrane biomimetic nanoparticles for inflammation and cancer targeting in drug delivery

Biomaterials Science, Год журнала: 2019, Номер 8(2), С. 552 - 568

Опубликована: Ноя. 11, 2019

Cell membrane coated nanoparticles have been designed for inflammation and cancer therapy. An array of cell membranes from library were extracted leveraged to coat a variety different diseases.

Язык: Английский

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Recent Advances in Glucose‐Oxidase‐Based Nanocomposites for Tumor Therapy

Small, Год журнала: 2019, Номер 15(51)

Опубликована: Ноя. 20, 2019

Abstract Glucose oxidase (GOx) can react with intracellular glucose and oxygen (O 2 ) to produce hydrogen peroxide (H O gluconic acid, which cut off the nutrition source of cancer cells consequently inhibit their proliferation. Therefore, GOx is recognised as an ideal endogenous oxido‐reductase for starvation therapy. This process further regulate tumor microenvironment by increasing hypoxia acidity. Thus, offers new possibilities elaborate design multifunctional nanocomposites However, natural expensive prepare purify exhibits immunogenicity, short in vivo half‐life, systemic toxicity. Furthermore, highly prone degrade after exposure biological conditions. These intrinsic shortcomings will undoubtedly limit its biomedical applications. Accordingly, some nanocarriers be used protect from surrounding environment, thus controlling or preserving activity. A variety including hollow mesoporous silica nanoparticles, metal–organic frameworks, organic polymers, magnetic nanoparticles are summarized construction GOx‐based multimodal synergistic In addition, current challenges promising developments this area highlighted.

Язык: Английский

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Therapeutic Polymersome Nanoreactors with Tumor-Specific Activable Cascade Reactions for Cooperative Cancer Therapy

ACS Nano, Год журнала: 2019, Номер unknown

Опубликована: Янв. 30, 2019

Therapeutic nanoreactors are of increasing interest in precise cancer therapy, which have been explored to situ produce therapeutic compounds from inert prodrugs or intrinsic molecules at the target sites. However, engineering a nanoreactor with tumor activable cascade reactions for efficient cooperative therapy remains great challenge. Herein, we demonstrate polymersome acidity-responsive membrane permeability activate orchestrated treatment. The constructed responsive polyprodrug polymersomes incorporating ultrasmall iron oxide nanoparticles and glucose oxidase membranes inner aqueous cavities, respectively. including consumption generate H2O2, accelerated ion release, Fenton reaction between H2O2 hydroxyl radicals (•OH), •OH-triggered rapid release parent drugs can be specifically activated by permeability. During this process, starving chemodynamic chemotherapy is realized high-efficiency suppression consumed produced compounds. design tumor-activable represents an insightful paradigm therapy.

Язык: Английский

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