Type-I AIE Photosensitizer Loaded Biomimetic System Boosting Cuproptosis to Inhibit Breast Cancer Metastasis and Rechallenge

ACS Nano, Год журнала: 2023, Номер 17(11), С. 10206 - 10217

Опубликована: Май 15, 2023

Cuproptosis shows good application prospects in tumor therapy. However, the copper efflux mechanism and highly expressed intracellular reducing substances can inhibit cuproptosis effects. In this study, a platelet vesicle (PV) coated cuprous oxide nanoparticle (Cu2O)/TBP-2 sensitization system (PTC) was constructed for multiple induction of cuproptosis. PTC prepared by physical extrusion AIE photosensitizer (TBP-2), Cu2O, PV. After biomimetic modification, enhance its long-term blood circulation targeting ability. Subsequently, rapidly degraded to release ions under acid conditions hydrogen peroxides cells. Then, light irradiation, TBP-2 quickly enters cell membrane generates hydroxyl radicals consume glutathione efflux. Accumulated cause lipoylated protein aggregation iron–sulfur loss, which result proteotoxic stress ultimately treatment target induce cells vitro vivo, significantly lung metastasis breast cancer, increase number central memory T peripheral blood, prevent rechallenge. It provides an idea design nanomedicine based on

Язык: Английский

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Harnessing Nanomaterials for Cancer Sonodynamic Immunotherapy

Advanced Materials, Год журнала: 2023, Номер 35(33)

Опубликована: Март 7, 2023

Abstract Immunotherapy has made remarkable strides in cancer therapy over the past decade. However, such emerging still suffers from low response rates and immune‐related adverse events. Various strategies have been developed to overcome these serious challenges. Therein, sonodynamic (SDT), as a non‐invasive treatment, received ever‐increasing attention especially treatment of deep‐seated tumors. Significantly, SDT can effectively induce immunogenic cell death trigger systemic anti‐tumor immune response, termed immunotherapy. The rapid development nanotechnology revolutionized effects with robust induction. As result, more innovative nanosonosensitizers synergistic modalities are established superior efficacy safe profile. In this review, recent advances immunotherapy summarized particular emphasis on how be explored harness for amplifying response. Moreover, current challenges field prospects its clinical translation also presented. It is anticipated that review provide rational guidance facilitate nanomaterials‐assisted immunotherapy, helping pave way next‐generation eventually achieve durable patients.

Язык: Английский

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Semiconducting Polymer Nanoparticles with Surface‐Mimicking Protein Secondary Structure as Lysosome‐Targeting Chimaeras for Self‐Synergistic Cancer Immunotherapy

Advanced Materials, Год журнала: 2022, Номер 34(31)

Опубликована: Июнь 15, 2022

Immunotherapy has received tremendous attention for tumor treatment, but the efficacy is greatly hindered by insufficient tumor-infiltration of immune cells and immunosuppressive microenvironment. The strategy that can efficiently activate cytotoxic T lymphocytes inhibit negative regulators will amplify immunotherapy outcome, which however very rare. Herein, a new kind semiconducting polymer (SP) nanoparticles developed, featured with surface-mimicking protein secondary structure (SPSS NPs) self-synergistic cancer combining immunogenic cell death (ICD) checkpoint blockade therapy. SPs excellent photodynamic property are synthesized rational fluorination, massively induce ICD. Additionally, peptide antagonists introduced self-assembled into β-sheet structures on NP surface via preparation process optimization, function as efficient lysosome-targeting chimaeras (LYTACs) to mediate degradation programmed ligand-1 (PD-L1) in lysosome. In vivo experiments demonstrate SPSS NPs not only elicit strong antitumor immunity suppress both primary distant tumor, also evoke long-term immunological memory against rechallenge. This work introduces robust agents well-designed photosensitizer-based ICD induction structures-mediated LYTAC-like multivalence PD-L1 blockade, rendering great promise synergistic immunotherapy.

Язык: Английский

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Bioorthogonal-Activated In Situ Vaccine Mediated by a COF-Based Catalytic Platform for Potent Cancer Immunotherapy

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(9), С. 5330 - 5341

Опубликована: Фев. 23, 2023

Personalized tumor vaccines have become a promising modality for cancer immunotherapy. However, in situ personalized generated from immunogenic cell death (ICD) and adjuvants are mired by toxic side effects unsatisfactory efficiency. Herein, functionalizing the reticular structure to optimize catalytic activity of materials, series biocompatible covalent organic framework (COF)-based catalysts been designed screened establishing bioorthogonal-activated vaccine an efficient safe way. Especially, pro-doxorubicin (pro-DOX) could be bioorthogonally activated COF-based Fe(II) catalysts, which elicited ICD released tumor-associated antigens (TAAs). This prodrug activation strategy minimize drug maximize treatment effects. More importantly, system also catalytically activate pro-imiquimod (pro-IMQ, TLR7/8 immune agonist), served as adjuvant amplify antitumor immunity. Notably, this not only facilitated strong response but prevented dose-dependent chemotherapeutic drugs, including systemic inflammation caused random distribution adjuvants. To best our knowledge, it is first time devise platform generating vaccine, would provide paradigm achieving secure robust

Язык: Английский

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Current advance of nanotechnology in diagnosis and treatment for malignant tumors

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Авг. 12, 2024

Cancer remains a significant risk to human health. Nanomedicine is new multidisciplinary field that garnering lot of interest and investigation. shows great potential for cancer diagnosis treatment. Specifically engineered nanoparticles can be employed as contrast agents in diagnostics enable high sensitivity high-resolution tumor detection by imaging examinations. Novel approaches labeling are also made possible the use nanoprobes nanobiosensors. The achievement targeted medication delivery therapy accomplished through rational design manufacture nanodrug carriers. Nanoparticles have capability effectively transport medications or gene fragments tissues via passive active targeting processes, thus enhancing treatment outcomes while minimizing harm healthy tissues. Simultaneously, context radiation sensitization photothermal enhance therapeutic efficacy malignant tumors. This review presents literature overview summary how nanotechnology used According oncological diseases originating from different systems body combining pathophysiological features cancers at sites, we most recent developments applications. Finally, briefly discuss prospects challenges cancer.

Язык: Английский

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Nano-drug delivery system targeting tumor microenvironment: A prospective strategy for melanoma treatment

Cancer Letters, Год журнала: 2023, Номер 574, С. 216397 - 216397

Опубликована: Сен. 18, 2023

Язык: Английский

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Extracellular Vesicles‐Derived Hybrid Nanoplatforms for Amplified CD47 Blockade‐Based Cancer Immunotherapy

Advanced Materials, Год журнала: 2023, Номер 35(35)

Опубликована: Июнь 29, 2023

Immunomodulation of tumor-associated macrophages (TAMs) into tumor-inhibiting M1-like phenotype is a promising but challenging strategy. Cleverly, tumor cells overexpress CD47, "don't eat me" signal that ligates with the regulatory protein alpha (SIRPα) on to escape phagocytosis. Thus, effective re-education TAMs "eat type and blocking CD47-SIRPα signaling play pivotal roles in immunotherapy. Herein, it reported hybrid nanovesicles (hEL-RS17) derived from extracellular vesicles M1 decorated RS17 peptide, an antitumor peptide specifically binds CD47 blocks signaling, can actively target remodel TAM phenotypes. Consequently, more infiltrate tissue phagocytize due blockade. By further co-encapsulating chemotherapeutic agent shikonin, photosensitizer IR820, immunomodulator polymetformin hEL-RS17, enhanced effect obtained combinational treatment modality close synergy among each component. Upon laser irradiation, designed SPI@hEL-RS17 nanoparticles exert potent efficacy against both 4T1 breast B16F10 melanoma models, which not only suppresses primary growth also inhibits lung metastasis prevents recurrence, exhibiting great potential boosting blockade-based

Язык: Английский

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Lipid Nanoparticles Optimized for Targeting and Release of Nucleic Acid

Advanced Materials, Год журнала: 2023, Номер 36(4)

Опубликована: Авг. 7, 2023

Abstract Lipid nanoparticles (LNPs) are currently the most promising clinical nucleic acids drug delivery vehicles. LNPs prevent degradation of cargo during blood circulation. Upon entry into cell, specific components lipid can promote endosomal escape acids. These basic properties as acid carriers. As exhibit hepatic aggregation characteristics, enhancing targeting out liver is a crucial way to improve administrated in vivo. Meanwhile, loaded often considered inadequate, and therefore, much effort devoted intracellular release efficiency Here, different strategies efficiently deliver from concluded their mechanisms investigated. In addition, based on information that trials or have completed trials, issues necessary be approached translation discussed, which it hoped will shed light development LNP drugs.

Язык: Английский

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Simultaneous Activation of Pyroptosis and cGAS‐STING Pathway with Epigenetic/ Photodynamic Nanotheranostic for Enhanced Tumor Photoimmunotherapy

Advanced Materials, Год журнала: 2023, Номер 36(7)

Опубликована: Окт. 5, 2023

Promoting innate immunity through pyroptosis induction or the cyclic GMP-AMP synthase-stimulator of interferon gene (cGAS-STING) pathway activation has emerged as a potent approach to counteract immunosuppressive tumor microenvironment and elicit systemic antitumor immunity. However, current inducers STING agonists often suffer from limitations including instability, unpredictable side effects, inadequate intracellular expression gasdermin STING. Here, tumor-specific nanotheranostic platform that combines photodynamic therapy (PDT) with epigenetic simultaneously activate cGAS-STING in light-controlled manner is constructed. This involves development oxidation-sensitive nanoparticles (NP1) loaded photosensitizer TBE, along decitabine nanomicelles (NP2). NP2 enables restoration E (GSDME) expression, while NP1-mediated PDT facilitates release DNA fragments damaged mitochondria potentiate pathway, promotes caspase-3 cleave upregulated GSDME into pore-forming GSDME-N terminal. Subsequently, released inflammatory cytokines facilitate maturation antigen-presentation cells, triggering T cell-mediated Overall, this study presents an elaborate strategy for simultaneous photoactivation enabling targeted photoimmunotherapy immunotolerant tumors. innovative holds significant promise overcoming associated existing therapeutic modalities represents valuable avenue future clinical applications.

Язык: Английский

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Nanocatalysts for modulating antitumor immunity: fabrication, mechanisms and applications

Chemical Society Reviews, Год журнала: 2024, Номер 53(5), С. 2643 - 2692

Опубликована: Янв. 1, 2024

This review discusses the structures and engineering strategies of nanocatalysts, highlighting their underlying mechanisms applications in cancer immunotherapy.

Язык: Английский

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