Tumor associated macrophages reprogrammed by targeted bifunctional bioorthogonal nanozymes for enhanced tumor immunotherapy

Wei, Yue; Wu, Si; Liu, Zhenqi; Niu, Jingsheng; Ren, Jinsong; Qu, Xiaogang

doi:10.1016/j.mattod.2022.01.024

Cited by 38 publications

(35 citation statements)

References 63 publications

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“…We then employed Amplex red assay to evaluate the intracelluar H 2 O 2 level after the OH-CPT treatment. Amplex Red acted as a specific H 2 O 2 probe, which could efficiently produce intensive red fluorescence when reacted with H 2 O 2 in the presence of peroxidase. , As revealed in Figure S24, the red fluorescence was observed in the OH-CPT treated group, suggesting the successful intracellular H 2 O 2 replenishment, which could amplify the Fe 3+ -based CDT. The synergistic elevated intracellular oxidative stress induced by the synthesized OH-CPT was further monitored by DCFH-DA fluorescent probe.…”

Section: Resultsmentioning

confidence: 94%

A Cell Selective Fluoride-Activated MOF Biomimetic Platform for Prodrug Synthesis and Enhanced Synergistic Cancer Therapy

Zhang

Liu

et al. 2022

ACS Nano

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As a burgeoning bioorthogonal reaction, the fluoride-mediated desilylation is capable of prodrug activation. However, due to the reactions lack of cell selectivity and unitary therapy modality, this strongly impedes their biomedical applications. Herein, we construct a cancer cell-selective biomimetic metal−organic framework (MOF)-F platform for prodrug activation and enhanced synergistic chemodynamic therapy (CDT). With cancer cell membranes camouflage, the designed biomimetic nanocatalyst displays preferential accumulation to homotypic cancer cells. Then, pH-responsive nanocatalyst releases fluoride ions and ferric ions. For activation of our designed prodrug tert-butyldimethyl silyl (TBS)-hydroxycamptothecin (TBSO-CPT), fluoride ions can desilylate TBS and cleave the designed silyl ether linker to synthesize the OH-CPT (10-hydroxycamptothecin) drug molecule, which effectively kills cancer cells. Intriguingly, the bioorthogonal-synthesized OH-CPT drug upregulates intracellular H 2 O 2 by activating nicotinamide adenine dinucleotide phosphate oxidase (NOX), amplifying the released iron induced Fenton reaction for synergistic CDT. Both in vitro and in vivo studies demonstrate our strategy presents a versatile fluoride-activated bioorthogonal catalyst for cancer cell-selective drug synthesis. Our work may accelerate the biomedical applications of fluoride-activated bioorthogonal chemistry.

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Section: Resultsmentioning

confidence: 94%

A Cell Selective Fluoride-Activated MOF Biomimetic Platform for Prodrug Synthesis and Enhanced Synergistic Cancer Therapy

Zhang

Liu

et al. 2022

ACS Nano

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“…In a different context, complex systems containing MoS2 sheets were demonstrated to provoke inflammatory responses eventually exploited to trigger oxidative damages on bacteria or cancer cells towards the development of efficient antibacterial and cancer therapies. [64,65] Scrolling MoS2 sheets in biomimetic and biological media could be harnessed for future applications. Further studies enquiring on the stability of the nanoscrolls should be conducted to prove that this can constitute a protective mechanism of the structure and be at the source of the inertness of the materials.…”

Section: Discussionmentioning

confidence: 99%

Resolution of MoS2 nanosheets-induced pulmonary inflammation driven by nanoscale intracellular transformation and extracellular-vesicle shuttles

Peña

Cherukula

Even

et al. 2022

Preprint

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Pulmonary exposure to some engineered nanomaterials can cause chronic lesions as a result of unresolved inflammation. Among two-dimensional (2D) nanomaterials and graphene, MoS2 have received tremendous attention in optoelectronics and nanomedicine. Here we propose an integrated approach to follow up the transformation of MoS2 nanosheets at the nanoscale and their impact on the lung inflammation status over one month after a single inhalation in mice. Analysis of immune cells, alveolar macrophages, extracellular vesicles, and cytokine profiling in bronchoalveolar lavage fluid (BALF) showed that MoS2 nanosheets induced initiation of lung inflammation that was rapidly resolved despite the persistence of various biotransformed molybdenum-containing nanostructures in alveolar macrophages and extracellular vesicles up to one month. Using in situ liquid phase transmission electron microscopy experiments, we could evidence the dynamics of MoS2 nanosheets transformation triggered by reactive oxygen species. Three main transformation mechanisms were observed directly at the nanoscale level: 1) scrolling of the dispersed sheets leading to the formation of nanoscrolls and folded patches, 2) etching releasing soluble MoO4-, and 3) oxidation generating oxidized sheet fragments. Extracellular vesicles released in BALF were also identified as a potential shuttle of MoS2 nanostructures and their degradation products and more importantly as mediators of inflammation resolution.

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“…Collectively, this study reveals that bioorthogonal nanozymes with bioorthogonal catalytic activity and natural enzyme-like activity are extremely prospective for cancer immunotherapy and can integrate multi-synergistic benefits into a single system, which represents a new approach for cancer immunotherapy. 39 Recently, in valuable research about revealing the antitumor immune function of pyroptosis, Liu and Shao et al designed a bioorthogonal catalytic system where phenylalanine trifluoroborate (Phe-BF 3 ) could enter the tumor cells and specifically catalyze the release of the active gasdermin from the Au nanoparticle-conjugated gasdermin. 87 Although TMC-based nanozymes were not used as catalysts in this bioorthogonal catalytic system, this work reflected the importance of bioorthogonal catalysis in the study of biological processes such as cell death and immunity, as well as provided the new directions for applying bioorthogonal chemistry to cancer immunotherapy.…”

Section: Bioorthogonal Nanozymes Mediated Cancer Immunotherapymentioning

confidence: 99%

Section: Tmc-based Bioorthognal Nanozymes For Therapeutic Applicationsmentioning

confidence: 99%

Bioorthogonal nanozymes: an emerging strategy for disease therapy

Zhang,

Fan

2023

Nanoscale

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Tumor associated macrophages reprogrammed by targeted bifunctional bioorthogonal nanozymes for enhanced tumor immunotherapy

Cited by 38 publications

References 63 publications

A Cell Selective Fluoride-Activated MOF Biomimetic Platform for Prodrug Synthesis and Enhanced Synergistic Cancer Therapy

A Cell Selective Fluoride-Activated MOF Biomimetic Platform for Prodrug Synthesis and Enhanced Synergistic Cancer Therapy

Resolution of MoS2 nanosheets-induced pulmonary inflammation driven by nanoscale intracellular transformation and extracellular-vesicle shuttles

Bioorthogonal nanozymes: an emerging strategy for disease therapy

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