Self‐Destructive Copper Carriers Induce Pyroptosis and Cuproptosis for Efficient Tumor Immunotherapy Against Dormant and Recurrent Tumors

Advanced Materials, Journal Year: 2023, Volume and Issue: 36(8)

Published: Oct. 11, 2023

Abstract Activating the strong immune system is a key initiative to counteract dormant tumors and prevent recurrence. Herein, self‐destructive multienzymatically active copper‐quinone‐GOx nanoparticles (abbreviated as CQG NPs) have been designed induce harmonious balanced pyroptosis cuproptosis using “Tai Chi mindset” awaken response for suppressing recurrent tumors. This cleverly material can disrupt antioxidant defense mechanism of tumor cells by inhibiting nuclear factor‐erythroid 2‐related factor 2 (NRF2)‐quinone oxidoreductase 1 (NQO1) signaling pathway. Furthermore, combined with its excellent multienzyme activity, it activates NOD‐like receptor protein 3 (NLRP3)‐mediated pyroptosis. Meanwhile, be triggered copper ions released from disintegration NPs sensitivity cancer enhanced through depletion endogenous chelators via Michael addition reaction between glutathione (GSH) quinone ligand, oxygen production catalase‐like reaction, starvation‐induced glucose deficiency. More importantly, NPs‐induced promote immunosuppressive microenvironment (TME) remodeling, enhance infiltration into tumor, activate robust systemic immunity. Collectively, this study provides new strategy resist dormancy, recurrence, improve clinical prognosis

Language: Английский

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Tumor Microenvironment‐Responsive Nanoparticles Amplifying STING Signaling Pathway for Cancer Immunotherapy

Advanced Materials, Journal Year: 2023, Volume and Issue: 36(6)

Published: Sept. 19, 2023

Abstract Insufficient activation of the stimulator interferon genes (STING) signaling pathway and profoundly immunosuppressive microenvironment largely limits effect cancer immunotherapy. Herein, tumor (TME)‐responsive nanoparticles (PMM NPs) are exploited that simultaneously harness STING Toll‐like receptor 4 (TLR4) to augment via TLR4‐mediated nuclear factor‐kappa B stimulation, leading increased secretion type I interferons (i.e., 4.0‐fold enhancement IFN‐β) pro‐inflammatory cytokines promote a specific T cell immune response. Moreover, PMM NPs relieve immunosuppression TME by decreasing percentage regulatory cells, polarizing M2 macrophages M1 type, thus creating an immune‐supportive unleash cascade adaptive Combined with anti‐PD‐1 antibody, synergistic efficacy is achieved in both inflamed colorectal noninflamed metastatic breast models. rechallenging tumor‐free animals homotypic cells induced complete rejection, indicating generation systemic antitumor memory. These TME‐responsive may open new avenue achieve spatiotemporal orchestration activation, providing promising clinical candidate for next‐generation

Language: Английский

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Leveraging Semiconducting Polymer Nanoparticles for Combination Cancer Immunotherapy

Advanced Materials, Journal Year: 2023, Volume and Issue: 36(1)

Published: Oct. 21, 2023

Abstract Cancer immunotherapy has become a promising method for cancer treatment, bringing hope to advanced patients. However, immune‐related adverse events caused by also bring heavy burden Semiconducting polymer nanoparticles (SPNs) as an emerging nanomaterial with high biocompatibility, can eliminate tumors and induce tumor immunogenic cell death through different therapeutic modalities, including photothermal therapy, photodynamic sonodynamic therapy. In addition, SPNs work functional nanocarrier synergize variety of immunomodulators amplify anti‐tumor immune responses. this review, SPNs‐based combination is comprehensively summarized according the SPNs’ modalities type loaded immunomodulators. The in‐depth understanding existing will hopefully inspire design more novel nanomaterials potent effects, ultimately promote their clinical translation.

Language: Английский

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Exosome‐Inhibiting Polymeric Sonosensitizer for Tumor‐Specific Sonodynamic Immunotherapy

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(25)

Published: March 6, 2024

Combination cancer immunotherapy based on electromagnetic energy and shows potent anti-cancer efficacy. However, as a factor that mediates tumor metastasis immune suppression, the impact of exosomes therapy under stimulation remains unclear. Herein, findings indicate sonodynamic (SDT) increases serum exosome levels by inducing apoptotic loosening extracellular matrix, promoting lung metastasis. To address this problem, an exosome-inhibiting polymeric sonosensitizer (EIPS) selectively inhibiting generation in response to biomarker is synthesized. EIPS consists semiconducting polymer backbone capable SDT poly(ethylene glycol) layer conjugated with tumor-specific enzyme-responsive inhibitor prodrug. After being cleaved Cathepsin B, releases active inhibitors, preventing exosome-mediated suppression As result, elicits robust antitumor effects through synergistic effect inhibition, completely establishing long-term memory effect. This first example showing combining inhibition can elicit without help typical agonists.

Language: Английский

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Engineered Bio‐Based Hydrogels for Cancer Immunotherapy

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(21)

Published: Feb. 16, 2024

Immunotherapy represents a revolutionary paradigm in cancer management, showcasing its potential to impede tumor metastasis and recurrence. Nonetheless, challenges including limited therapeutic efficacy severe immune-related side effects are frequently encountered, especially solid tumors. Hydrogels, class of versatile materials featuring well-hydrated structures widely used biomedicine, offer promising platform for encapsulating releasing small molecule drugs, biomacromolecules, cells controlled manner. Immunomodulatory hydrogels present unique capability augmenting immune activation mitigating systemic toxicity through encapsulation multiple components localized administration. Notably, based on biopolymers have gained significant interest owing their biocompatibility, environmental friendliness, ease production. This review delves into the recent advances bio-based immunotherapy synergistic combinatorial approaches, highlighting diverse applications. It is anticipated that this will guide rational design field immunotherapy, fostering clinical translation ultimately benefiting patients.

Language: Английский

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Remote Control of Energy Transformation‐Based Cancer Imaging and Therapy

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(27)

Published: March 29, 2024

Cancer treatment requires precise tumor-specific targeting at specific sites that allows for high-resolution diagnostic imaging and long-term patient-tailorable cancer therapy; while, minimizing side effects largely arising from non-targetability. This can be realized by harnessing exogenous remote stimuli, such as tissue-penetrative ultrasound, magnetic field, light, radiation, enable local activation therapy in deep tumors. A myriad of nanomedicines efficiently activated when the energy stimuli transformed into another type energy. review discusses control transformation targetable, efficient, therapy. Such ultrasonic, magnetic, photonic, radiative, radioactive mechanical, thermal, chemical, radiative to a variety modalities. The current article describes multimodal where serial cascade or multiple types occur. includes not only hyperthermia, radiation but also emerging thermoelectric, pyroelectric, piezoelectric therapies treatment. It illustrates resonance, fluorescence, computed tomography, photoluminescence, photoacoustic imaging-guided therapies. highlights afterglow eliminate autofluorescence sustained signal emission after excitation.

Language: Английский

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Circulating immunotherapy strategy based on pyroptosis and STING pathway: Mn-loaded paclitaxel prodrug nanoplatform against tumor progression and metastasis

Biomaterials, Journal Year: 2024, Volume and Issue: 306, P. 122472 - 122472

Published: Jan. 23, 2024

Language: Английский

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Endoplasmic Reticulum‐Targeting Iridium(III) Nanosonosensitizer Amplifies Immunogenic Cell Death for Boosted Tumor Sono‐Immunotherapy

Advanced Functional Materials, Journal Year: 2024, Volume and Issue: 34(26)

Published: Feb. 27, 2024

Abstract Reactive oxygen species (ROS)‐induced endoplasmic reticulum (ER) stress in sonodynamic therapy (SDT) can elicit immunogenic cell death (ICD)‐initiated antitumor immunity for augmented sono‐immunotherapy. However, unsatisfactory activity and mediocre ER induction ability of sonosensitizers essentially restrict SDT efficacy ICD stimulation. Herein, a versatile ER‐targeting Iridium(III) nanosonosensitizer is developed as superior inducer boosted tumor An ingenious cholic acid (CA)‐functionalized sonosensitizer Ir‐CA well‐designed skillfully crosslinked with human serum albumin (HSA) to form HSA@Ir‐CA. With high stability, favorable tumor‐targeting ability, reduction‐responsiveness, HSA@Ir‐CA preferentially accumulates sites enhanced cellular uptake, followed by rapid disassembly responding intracellular reductive environment. The uncaged selectively accumulate precisely disrupt situ produced type I II ROS upon US irradiation high‐efficiency SDT. Moreover, the maximized eminently amplifies evoke robust systemic immunity, inhibiting growths primary/distant tumor, lung metastasis, recurrence. This combined immune checkpoint inhibitor (αPD‐L1) further achieves reinforced therapeutic outcome against immunologically “cold” tumor. study presents an effective paradigm optimize amplify ICD‐initiated responses

Language: Английский

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Black Phosphorus Quantum Dot Loaded Bioinspired Nanoplatform Synergized with aPD-L1 for Multimode Cancer Immunotherapy

Nano Letters, Journal Year: 2024, Volume and Issue: 24(22), P. 6767 - 6777

Published: May 21, 2024

Efforts to prolong the blood circulation time and bypass immune clearance play vital roles in improving therapeutic efficacy of nanoparticles (NPs). Herein, a multifunctional nanoplatform (BPP@RTL) that precisely targets tumor cells is fabricated by encapsulating ultrasmall phototherapeutic agent black phosphorus quantum dot (BPQD), chemotherapeutic drug paclitaxel (PTX), immunomodulator PolyMetformin (PM) hybrid membrane-camouflaged liposomes. Specifically, cell membrane coating derived from fusion cancer red displays excellent targeting efficiency long property due innate features both membranes. After collaboration with aPD-L1-based checkpoint blockade therapy, boosted immunotherapeutic effect obtained elevated dendritic maturation T activation. Significantly, laser-irradiated BPP@RTL combined aPD-L1 effectively eliminates primary tumors inhibits lung metastasis 4T1 breast model, offering promising treatment plan develop personalized antitumor strategy.

Language: Английский

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Self-Cascaded Pyroptosis-STING Initiators for Catalytic Metalloimmunotherapy

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 17, 2025

Gasdermin (GSDM)-mediated pyroptosis involves the induction of mitochondrial damage and subsequent release DNA (mtDNA), which is anticipated to activate cGAS-STING pathway, thereby augmenting antitumor immune response. However, challenges lie in effectively triggering cancer cells subsequently enhancing activation with specificity. Herein, we developed intelligent self-cascaded pyroptosis-STING initiators cobalt fluoride (CoF2) nanocatalysts for catalytic metalloimmunotherapy. CoF2 a semiconductor structure enzyme-like activity generated substantial amount reactive oxygen species (ROS) under stimulation by endogenous H2O2 exogenous ultrasound. Importantly, discovered that Co-based nanomaterials themselves induce cells. Therefore, initially acted as inducers, caspase-1/GSDMD-dependent via Co2+ ROS, leading mtDNA release. Subsequently, were further utilized STING agonists specifically capable detecting pathway. These cascade events triggered robust response, modulating immunosuppressive tumor microenvironment into an immune-supportive state, providing favorable support therapy. This innovative strategy not only significantly impeded growth primary but also elicited response augment efficacy checkpoint inhibitors preventing distant progression. Overall, this study proposed self-cascade activating amplifying pathway specificity mediated pyroptosis, representing valuable avenue future

Language: Английский

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