Cuproptosis Induced by ROS Responsive Nanoparticles with Elesclomol and Copper Combined with αPD‐L1 for Enhanced Cancer Immunotherapy

Advanced Materials, Год журнала: 2023, Номер 35(22)

Опубликована: Март 14, 2023

Cuproptosis is a new cell death that depends on copper (Cu) ionophores to transport Cu into cancer cells, which induces death. However, existing are small molecules with short blood half-life making it hard enough cells. Herein, reactive oxygen species (ROS)-sensitive polymer (PHPM) designed, used co-encapsulate elesclomol (ES) and form nanoparticles (NP@ESCu). After entering ES Cu, triggered by excessive intracellular ROS, readily released. work in concerted way not only kill cells cuproptosis, but also induce immune responses. In vitro, the ability of NP@ESCu efficiently cuproptosis investigated. addition, change transcriptomes treated explored RNA-Seq. vivo, found mice model subcutaneous bladder cancer, reprograming tumor microenvironment. Additionally, further combined anti-programmed protein ligand-1 antibody (αPD-L1). This study provides first report combining nanomedicine can αPD-L1 for enhanced therapy, thereby providing novel strategy future therapy.

Язык: Английский

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Acid‐Ionizable Iron Nanoadjuvant Augments STING Activation for Personalized Vaccination Immunotherapy of Cancer

Advanced Materials, Год журнала: 2022, Номер 35(10)

Опубликована: Дек. 28, 2022

The critical challenge for cancer vaccine-induced T-cell immunity is the sustained activation of antigen cross-presentation in antigen-presenting cells (APCs) with innate immune stimulation. In this study, it first discovered that clinically used magnetic contrast agents, iron oxide nanoparticles (IONPs), markedly augment type-I interferon (IFN-I) production profile stimulator genes (STING) agonist MSA-2 and achieve a 16-fold dosage-sparing effect human STING haplotype. Acid-ionizable copolymers are coassembled IONPs into nanoadjuvants to concentrate draining lymph nodes. top candidate nanoadjuvant (PEIM) efficiently delivers model ovalbumin (OVA) CD169+ APCs facilitates elicit 55-fold greater frequency antigen-specific CD8+ cytotoxic T-lymphocyte response than soluble antigen. PEIM@OVA nanovaccine immunization induces potent durable antitumor prevent tumor lung metastasis eliminate established tumors. Moreover, PEIM applicable deliver autologous synergizes checkpoint blockade therapy prevention postoperative recurrence distant B16-OVA melanoma MC38 colorectal models. acid-ionizable offers generalizable readily translatable strategy cascade personalized vaccination immunotherapy.

Язык: Английский

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Platinum Prodrug Nanoparticles with COX‐2 Inhibition Amplify Pyroptosis for Enhanced Chemotherapy and Immune Activation of Pancreatic Cancer

Advanced Materials, Год журнала: 2023, Номер 36(11)

Опубликована: Дек. 14, 2023

Pyroptosis, an emerging mechanism of programmed cell death, holds great potential to trigger a robust antitumor immune response. Platinum-based chemotherapeutic agents can induce pyroptosis via caspase-3 activation. However, these also enhance cyclooxygenase-2 (COX-2) expression in tumor tissues, leading drug resistance and evasion pancreatic cancer significantly limiting the effectiveness chemotherapy-induced pyroptosis. Here, amphiphilic polymer (denoted as PHDT-Pt-In) containing both indomethacin (In, COX-2 inhibitor) platinum(IV) prodrug (Pt(IV)) is developed, which responsive glutathione (GSH). This self-assemble into nanoparticles Pt-In NP) that disintegrate cells due GSH responsiveness, releasing In inhibit expression, hence overcoming chemoresistance amplifying cisplatin-induced mouse model, NP growth elicit innate adaptive responses. Moreover, when combined with anti-programmed death ligand (α-PD-L1) treatment, demonstrate ability completely suppress metastatic tumors, transforming "cold tumors" "hot tumors". Overall, sustained release Pt(IV) from amplifies platinum-drug-induced long-term responses, presenting generalizable strategy for cancer.

Язык: Английский

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Bioactivable STING Nanoagonists to Synergize NIR‐II Mild Photothermal Therapy Primed Robust and Long‐Term Anticancer Immunity

Advanced Materials, Год журнала: 2023, Номер 35(48)

Опубликована: Сен. 11, 2023

Pharmacological activation of the stimulator interferon genes (STING) pathway has become a promising strategy for cancer immunotherapy. However, insufficient tumorous accumulation, rapid clearance, and short duration drug efficacy in tumor microenvironment small structural STING agonists greatly compromise therapeutic efficacy. Herein, extracellular matrix (ECM) is presented anchoring agonist-based photoimmunothernostic nanomedicine (SAPTN) that can be activated by mild-temperature photothermal therapy (mild PTT) induced neutrophilic inflammation. The SAPTN owns second window near-infrared (NIR-II) photonics properties fitting NIR-II fluorescence photoacoustic imaging-guided therapy. aggregates targeting to ECM provide slow continuous release potent diABZIs. mild PTT long-lasting released synergistically prime systematic, robust, long-term anticancer immunity. In model, this approach leads complete eradication about 100% mice with orthotopic breast tumors, regained tumor-free survival at least 2 months. addition, immune-mediated abscopal effect shows inhibition distant solid growth intratumoral administration laser irradiation. Overall, represents generalized photoactivable immunity improved theranostics.

Язык: Английский

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Recent progress in MOFs-based nanozymes for biosensing

Nano Research, Год журнала: 2023, Номер 17(1), С. 39 - 64

Опубликована: Июль 6, 2023

Язык: Английский

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Decomposable Nanoagonists Enable NIR‐Elicited cGAS‐STING Activation for Tandem‐Amplified Photodynamic‐Metalloimmunotherapy

Advanced Materials, Год журнала: 2024, Номер 36(21)

Опубликована: Фев. 14, 2024

Activation of the cyclic GMP-AMP synthase-stimulator interferon genes (cGAS-STING) pathway has emerged as an efficient strategy to improve therapeutic outcomes immunotherapy. However, "constantly active" mode current STING agonist delivery strategies typically leads off-target toxicity and hyperimmunity. To address this critical issue, herein a metal-organic frameworks-based nanoagonist (DZ@A7) featuring tumor-specific near-infrared (NIR) light-enhanced decomposition is constructed for precisely localized activation photodynamic-metalloimmunotherapy. The engineered enabled generation mitochondria-targeted reactive oxygen species under NIR irradiation specifically release mitochondrial DNA (mtDNA) inhibit repair nuclear via hypoxia-responsive drugs. Oxidized tumor mtDNA serves endogenous danger-associated molecular pattern that activates cGAS-STING pathway. Concurrently, NIR-accelerated zinc ions overloading in cancer cells further enhance cGAS enzymatic activity through metalloimmune effects. By combining synergistically enhanced triggered by irradiation, facilitated maturation dendritic infiltration cytotoxic T lymphocytes primary eradication, which also established long-term anti-tumor immunity suppress metastasis. Therefore, developed NIR-triggered, agonist-free, tandem-amplified pathway, thereby offering distinct paradigm

Язык: Английский

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Immunological nanomaterials to combat cancer metastasis

Chemical Society Reviews, Год журнала: 2024, Номер 53(12), С. 6399 - 6444

Опубликована: Янв. 1, 2024

This review highlights recent advances in immunological nanomaterials against metastasis and summarizes various nanomaterial-mediated immunotherapy strategies.

Язык: Английский

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Development of tumor-evolution-targeted anticancer therapeutic nanomedicineEVT

Chem, Год журнала: 2024, Номер 10(5), С. 1337 - 1356

Опубликована: Янв. 25, 2024

Язык: Английский

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Alendronate Triggered Dual‐Cascade Targeting Prodrug Nanoparticles for Enhanced Tumor Penetration and STING Activation of Osteosarcoma

Advanced Functional Materials, Год журнала: 2023, Номер 33(49)

Опубликована: Сен. 3, 2023

Abstract The complex physiological environment in bone tissue poses a challenge to the efficient delivery of chemotherapeutic agents for osteosarcoma (OS) treatment; hence, an drug system designed OS is highly desired. Herein, alendronate (Ale)‐based cationic platinum prodrug nanoparticles (Ale NP) are developed, which exhibit cascade responsiveness tumor microenvironment. With Ale triggered targeting and charge reversal effects, NP demonstrates superior capacity achieving deep penetration into dense tissues. Furthermore, can induce dendritic cell (DC) maturation via activation cyclic GMP‐AMP synthase‐stimulator interferon genes (cGAS‐STING) pathway using drugs. potent phenanthridine (Pt(II)) be released presence overexpressed glutathione (GSH) cells, thereby dual‐targeted drugs OS. Notably, not only effectively eliminates internal region but also acts as STING agonist reverse suppressive microenvironment Overall, Ale‐triggered dual‐cascade significantly improve OS, hence paving promising avenue clinical treatment

Язык: Английский

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Targeting DNA Damage and Repair Machinery via Delivering WEE1 Inhibitor and Platinum (IV) Prodrugs to Stimulate STING Pathway for Maximizing Chemo‐Immunotherapy in Bladder Cancer

Advanced Materials, Год журнала: 2023, Номер 36(1)

Опубликована: Окт. 18, 2023

Abstract Both cisplatin‐based chemotherapy and immune checkpoint blockers (ICBs)‐based immunotherapy are the first‐line treatments for patients with advanced bladder cancer. Cancer cells can develop resistance to cisplatin through extensive DNA repair, while a low response rate ICBs is mostly due presence of an immunosuppressive microenvironment PD‐L1 expression. Herein, glutathione (GSH)‐responsive nanoparticle (NP2) loaded prodrug (Pt (IV)) WEE1 inhibitor (MK1775) designed. NP2 be triggered by GSH in cancer cells, released MK1775 inhibit activity protein, which ultimately increases damage cisplatin. Genome‐wide RNA sequencing first reveals that repair machinery interfering cell cycle significantly activate stimulator interferon genes pathway. Tumor growth inhibited vivo. As innate adaptive responses stimulated, modified, “immune cold tumor” transformed into hot tumor". In addition, upregulate expression tumor thereby increasing monoclonal antibody (αPD‐L1) eliciting long‐term both primary metastatic tumors.

Язык: Английский

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