Pyroptosis‐Mediated Synergistic Photodynamic and Photothermal Immunotherapy Enabled by a Tumor‐Membrane‐Targeted Photosensitive Dimer

Advanced Materials, Год журнала: 2023, Номер 35(25)

Опубликована: Март 15, 2023

Overcoming the resistance to apoptosis and immunosuppression of tumor cells is a significant challenge in augmenting effect cancer immunotherapy. Pyroptosis, lytic programmed cell-death pathway unlike apoptosis, considered type immunogenic cell death (ICD) that can intensify ICD process cells, releasing dramatically increased tumor-associated antigens damage-associated molecular patterns promote Herein, membrane-targeted aggregation-induced emission photosensitive dimer found be able achieve highly efficient under synergistic photodynamic photothermal therapy. The efficiently produce type-I reactive oxygen species (ROS) by therapy hypoxic tissue, leading pyroptosis direct membrane damage, which further reinforced its effect. Furthermore, enhanced based on completely eliminate primary seventh day treatment also boost systemic antitumor immunity generating immune memory, demonstrated superior therapeutic effects both solid tumors metastatic when healing 4T1 mouse models with poor immunogenicity.

Язык: Английский

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Tumor‐Microenvironment‐Activatable Polymer Nano‐Immunomodulator for Precision Cancer Photoimmunotherapy

Advanced Materials, Год журнала: 2021, Номер 34(8)

Опубликована: Дек. 2, 2021

Cancer nanomedicine combined with immunotherapy has become a promising strategy for treating cancer in terms of safety and potency; however, precise regulation the activation antitumor immunity remains challenging. Herein, smart semiconducting polymer nano-immunomodulator (SPNI), which responds to acidic tumor microenvironment (TME), precision photodynamic cancer, is reported. The SPNI self-assembled by near-infrared (NIR)-absorbing an amphipathic conjugated Toll-like receptor 7 (TLR7) agonist via acid-labile linker. Upon arrival at site, undergoes hydrolysis triggers efficient liberation TLR7 response TME dendritic cell activation. Moreover, exerts effects direct eradication immunogenic death under NIR photoirradiation. synergistic action released factors acidic-TME-activated can serve as situ generated vaccine evoke strong activities. Notably, such localized immune boosts systemic responses, resulting enhanced cytotoxic CD8+ T infiltration inhibit growth metastasis. Thereby, this work presents general devise prodrug immunotherapeutics immunotherapy.

Язык: Английский

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Nitric Oxide Induces Immunogenic Cell Death and Potentiates Cancer Immunotherapy

ACS Nano, Год журнала: 2022, Номер 16(3), С. 3881 - 3894

Опубликована: Март 3, 2022

Tumor cells undergoing immunogenic cell death (ICD) release damage-associated molecular patterns (DAMPs) to trigger a long-term protective antitumor response. ICD can be induced by certain pathogens, chemotherapeutics, and physical modalities. In this work, we demonstrate that gaseous molecule, specifically nitric oxide (NO), induce potent effect. NO exerts cytotoxic effects are accompanied the emission of DAMPs based on endoplasmic reticulum stress mitochondrial dysfunction pathways. Released elicit immunological protection against subsequent rechallenge syngeneic tumor in immunocompetent mice. We prepare polynitrosated polyesters with high storage capacity through facile polycondensation reaction followed postsynthetic modification. The polyesters-based nanogenerator (NanoNO) enables efficient delivery controlled tumors induces sufficient different immune-intact models tumors, NanoNO exhibits significant growth suppression increases local dose signals T infiltrations, ultimately prolonging survival. addition, synergizes PD-1 blockade prevent metastasis. conclude not only is inducer for cancer immunotherapy but also it expands range inducers into field molecules.

Язык: Английский

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Reactive oxygen species-powered cancer immunotherapy: Current status and challenges

Journal of Controlled Release, Год журнала: 2023, Номер 356, С. 623 - 648

Опубликована: Март 21, 2023

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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Nanozyme-mediated biocatalysis as a mitochondrial oxidative stress amplifier for tumor nanocatalytic immunotherapy

Chemical Engineering Journal, Год журнала: 2023, Номер 481, С. 148270 - 148270

Опубликована: Дек. 23, 2023

Язык: Английский

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Advanced strategies to evade the mononuclear phagocyte system clearance of nanomaterials

Exploration, Год журнала: 2023, Номер 3(1)

Опубликована: Янв. 5, 2023

Nanomaterials are promising carriers to improve the bioavailability and therapeutic efficiency of drugs by providing preferential drug accumulation at their sites action, but delivery efficacy is severely limited a series biological barriers, especially mononuclear phagocytic system (MPS)-the first major barrier encountered systemically administered nanomaterials. Herein, current strategies for evading MPS clearance nanomaterials summarized. First, engineering methods including surface modification, cell hitchhiking, physiological environment modulation reduce explored. Second, disabling blockade, suppression macrophage phagocytosis, macrophages depletion examined. Last, challenges opportunities in this field further discussed.

Язык: Английский

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Dual‐Cascade Activatable Nanopotentiators Reshaping Adenosine Metabolism for Sono‐Chemodynamic‐Immunotherapy of Deep Tumors

Advanced Science, Год журнала: 2023, Номер 10(10)

Опубликована: Фев. 2, 2023

Immunotherapy is an attractive treatment strategy for cancer, while its efficiency and safety need to be improved. A dual-cascade activatable nanopotentiator sonodynamic therapy (SDT) chemodynamic (CDT)-cooperated immunotherapy of deep tumors via reshaping adenosine metabolism herein reported. This (NPMCA) constructed through crosslinking deaminase (ADA) with chlorin e6 (Ce6)-conjugated manganese dioxide (MnO2) nanoparticles a reactive oxygen species (ROS)-cleavable linker. In the tumor microenvironment ultrasound (US) irradiation, NPMCA mediates CDT SDT concurrently in covered 2-cm tissues produce abundant ROS, which results scissoring ROS-cleavable linkers activate ADA within NCMCA block metabolism. Moreover, immunogenic cell death (ICD) dying cells upregulation stimulator interferon genes (STING) triggered by generated ROS Mn2+ from NPMCA, respectively, leading activation antitumor immune response. The potency response further reinforced reducing accumulation activated ADA. As result, enables SDT-cooperated immunotherapy, showing obviously improved therapeutic efficacy inhibit growths bilateral tumors, primary are tissues.

Язык: Английский

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In situ Engineering of Tumor‐Associated Macrophages via a Nanodrug‐Delivering‐Drug (β‐Elemene@Stanene) Strategy for Enhanced Cancer Chemo‐Immunotherapy

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(41)

Опубликована: Июнь 29, 2023

Tumor-associated macrophages (TAMs) play a critical role in the immunosuppressive solid tumor microenvironment (TME), yet situ engineering of TAMs for enhanced immunotherapy remains significant challenge translational immuno-oncology. Here, we report an innovative nanodrug-delivering-drug (STNSP@ELE) strategy that leverages two-dimensional (2D) stanene-based nanosheets (STNSP) and β-Elemene (ELE), small-molecule anticancer drug, to overcome TAM-mediated immunosuppression improve chemo-immunotherapy. Our results demonstrate both STNSP ELE are capable polarizing tumor-supportive M2-like into tumor-suppressive M1-like phenotype, which acts with chemotherapeutic boost antitumor responses. In vivo mouse studies STNSP@ELE treatment can reprogram TME by significantly increasing intratumoral ratio M1/M2-like TAMs, enhancing population CD4+ CD8+ T lymphocytes mature dendritic cells, elevating expression immunostimulatory cytokines B16F10 melanomas, thereby promoting robust response. study not only demonstrates chemo-immunotherapeutic nanoplatform has immune-modulatory capabilities tumors, but also highlights promise this developing other nano-immunotherapeutics treating various types tumors.

Язык: Английский

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Delivering metal ions by nanomaterials: Turning metal ions into drug-like cancer theranostic agents

Coordination Chemistry Reviews, Год журнала: 2023, Номер 494, С. 215332 - 215332

Опубликована: Июль 17, 2023

Язык: Английский

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