Manganese‐Based Tumor Immunotherapy

Advanced Materials, Год журнала: 2022, Номер 35(19)

Опубликована: Сен. 19, 2022

Abstract As an essential micronutrient, manganese (Mn) participates in various physiological processes and plays important roles host immune system, hematopoiesis, endocrine function, oxidative stress regulation. Mn‐based nanoparticles are considered to be biocompatible show versatile applications nanomedicine, particular utilized tumor immunotherapy the following ways: 1) acting as a nanocarrier deliver immunotherapeutic agents for immunotherapy; 2) serving adjuvant regulate microenvironment enhance 3) activating host's system through cGAS‐STING pathway trigger 4) real‐time monitoring effect by magnetic resonance imaging (MRI) since Mn 2+ ions ideal MRI contrast agent which can significantly T 1 ‐weighted signal after binding proteins. This comprehensive review focuses on most recent progress of nanoplatforms immunotherapy. The characteristics first discussed guide design multifunctional nanoplatforms. Then biomedical nanoplatforms, including alone, immunotherapy‐involved multimodal synergistic therapy, imaging‐guided detail. Finally, challenges future developments highlighted.

Язык: Английский

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Gas therapy potentiates aggregation-induced emission luminogen-based photoimmunotherapy of poorly immunogenic tumors through cGAS-STING pathway activation

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Май 23, 2023

The immunologically "cold" microenvironment of triple negative breast cancer results in resistance to current immunotherapy. Here, we reveal the immunoadjuvant property gas therapy with cyclic GMP-AMP synthase-stimulator interferon genes (cGAS-STING) pathway activation augment aggregation-induced emission (AIE)-active luminogen (AIEgen)-based photoimmunotherapy. A virus-mimicking hollow mesoporous tetrasulfide-doped organosilica is developed for co-encapsulation AIEgen and manganese carbonyl fabricate nanoadjuvant. As tetra-sulfide bonds are responsive intratumoral glutathione, nanoadjuvant achieves tumor-specific drug release, promotes photodynamic therapy, produces hydrogen sulfide (H2S). Upon near-infrared laser irradiation, AIEgen-mediated phototherapy triggers burst carbon monoxide (CO)/Mn2+. Both H2S CO can destroy mitochondrial integrity induce leakage DNA into cytoplasm, serving as immunoadjuvants activate cGAS-STING pathway. Meanwhile, Mn2+ sensitize cGAS STING-mediated type I production. Consequently, potentiates photoimmunotherapy poorly immunogenic tumors female mice.

Язык: Английский

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A protein-based cGAS-STING nanoagonist enhances T cell-mediated anti-tumor immune responses

Nature Communications, Год журнала: 2022, Номер 13(1)

Опубликована: Сен. 28, 2022

Abstract cGAS-STING pathway is a key DNA-sensing machinery and emerges as promising target to overcome the immunoresistance of solid tumors. Here we describe bovine serum albumin (BSA)/ferritin-based nanoagonist incorporating manganese (II) ions β-lapachone, which cooperatively activates signaling in dendritic cells (DCs) elicit robust adaptive antitumor immunity. Mn 2+ -anchored mannose-modified BSAs β-lapachone-loaded ferritins are crosslinked afford bioresponsive protein nanoassemblies, dissociate into monodispersive units acidic perivascular tumor microenvironment (TME), thus enabling enhanced penetration spatiotemporally controlled β-lapachone delivery DCs cells, respectively. causes immunogenic cell apoptosis releases abundant dsDNA TME, while enhances sensitivity cGAS augments STING trigger downstream immunostimulatory signals. The tumor-specific T cell-mediated immune response against poorly tumors vivo, offering approach for immunotherapy clinics.

Язык: Английский

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Manganese-phenolic nanoadjuvant combines sonodynamic therapy with cGAS-STING activation for enhanced cancer immunotherapy

Nano Today, Год журнала: 2022, Номер 43, С. 101405 - 101405

Опубликована: Янв. 25, 2022

Язык: Английский

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Bioactive inorganic nanomaterials for cancer theranostics

Chemical Society Reviews, Год журнала: 2023, Номер 52(6), С. 2031 - 2081

Опубликована: Янв. 1, 2023

Bioactive materials are a special class of biomaterials that can react in vivo to induce biological response or regulate functions, thus achieving better curative effect than traditional inert biomaterials. For cancer theranostics, compared with organic polymer nanomaterials, inorganic nanomaterials possess unique physical and chemical properties, have stronger mechanical stability on the basis maintaining certain bioactivity, easy be compounded various carriers (polymer carriers, etc.), so as achieve specific antitumor efficacy. After entering nanoscale, due nano-size effect, high surface area nanostructures, exhibit effects, which significantly influence interaction organisms. Therefore, research applications bioactive theranostics attracted wide attention. In this review, we mainly summarize recent progress also introduce definition, synthesis modification strategies nanomaterials. Thereafter, tumor imaging therapy, including microenvironment (TME) regulation, catalytic gas regulatory cell death immunotherapy, discussed. Finally, biosafety challenges mentioned, their future development opportunities prospected. This review highlights bioapplication

Язык: Английский

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Recent progress of metal‐based nanomaterials with anti‐tumor biological effects for enhanced cancer therapy

Exploration, Год журнала: 2023, Номер 3(5)

Опубликована: Июнь 30, 2023

Abstract Metal‐based nanomaterials have attracted broad attention recently due to their unique biological physical and chemical properties after entering tumor cells, namely effects. In particular, the abilities of Ca 2+ modulate T cell receptors activation, K + regulate stem differentiation, Mn activate STING pathway, Fe 2+/3+ induce ferroptosis enhance catalytic therapy, make metal ions metal‐based play crucial roles in cancer treatments. Therefore, superior advantages characteristics microenvironment, we will summarize recent progress anti‐tumor effects nanomaterials. Based on different this review mainly focuses following five aspects: (1) metal‐enhanced radiotherapy sensitization, (2) (3) ferroptosis, (4) pyroptosis, (5) immunotherapy. At same time, shortcomings therapy are also discussed, future research directions been prospected. The highlights promising biosafety, potent efficacy for in‐depth various mechanism studies provide novel ideas application

Язык: Английский

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Biomineralized MnO₂ Nanoplatforms Mediated Delivery of Immune Checkpoint Inhibitors with STING Pathway Activation to Potentiate Cancer Radio-Immunotherapy

ACS Nano, Год журнала: 2023, Номер 17(5), С. 4495 - 4506

Опубликована: Фев. 27, 2023

Radiotherapy (RT), as one of the main methods in clinical treatment various malignant tumors, would induce systemic immunotherapeutic effects by triggering immunogenic cell death (ICD) cancer cells. However, antitumor immune responses produced RT-induced ICD alone usually are not robust enough to eliminate distant tumors and thus ineffective against metastases. Herein, a biomimetic mineralization method for facile synthesis MnO2 nanoparticles with high anti-programmed ligand 1 (αPDL1) encapsulation efficiency (αPDL1@MnO2) is proposed reinforce responses. This therapeutic nanoplatforms-mediated RT can significantly improve killing tumor cells effectively evoke overcoming hypoxia-induced radio-resistance reprogramming immunosuppressive microenvironment (TME). Furthermore, released Mn2+ ions from αPDL1@MnO2 under acidic pH activate cyclic GMP-AMP synthase (cGAS)-stimulator interferon genes (STING) pathway facilitate dendritic (DCs) maturation. Meanwhile, αPDL1 further promote intratumoral infiltration cytotoxic T lymphocytes (CTLs) trigger responses, resulting strong abscopal effect inhibit Overall, biomineralized MnO2-based nanoplatforms offer simple strategy TME modulation activation, which promising enhanced immunotherapy.

Язык: Английский

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Nanoparticle‐Mediated Radiotherapy Remodels the Tumor Microenvironment to Enhance Antitumor Efficacy

Advanced Materials, Год журнала: 2022, Номер 35(21)

Опубликована: Дек. 16, 2022

Radiotherapy (RT) uses ionizing radiation to eradicate localized tumors and, in rare cases, control outside of the irradiated fields via stimulating an antitumor immune response (abscopal effect). However, therapeutic effect RT is often limited by inherent physiological barriers tumor microenvironment (TME), such as hypoxia, abnormal vasculature, dense extracellular matrix (ECM), and immunosuppressive TME. Thus, it critical develop new strategies that can remodel TME overcome radio-resistance suppression. In past decade, high-Z-element nanoparticles have been developed increase radiotherapeutic indices reducing X-ray doses side effects normal tissues enhance abscopal activating elicit systemic immunity. this review, principles radiosensitization, mechanisms suppression, use various sensitize TMEs for enhanced efficacy are discussed. The challenges clinical translation multifunctional TME-remodeling nanoradiosensitizers also highlighted.

Язык: Английский

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Manganese Coordination Micelles That Activate Stimulator of Interferon Genes and Capture In Situ Tumor Antigens for Cancer Metalloimmunotherapy

ACS Nano, Год журнала: 2022, Номер 16(10), С. 16909 - 16923

Опубликована: Окт. 6, 2022

Cancer immunotherapy holds great promise but is generally limited by insufficient induction of anticancer immune responses. Here, a metal micellar nanovaccine developed the self-assembly manganese (Mn), stimulator interferon genes (STING) agonist (ABZI) and naphthalocyanine (ONc) coordinated nanoparticles (ONc-Mn-A) in maleimide-modified Pluronic F127 (malF127) micelles. Owing to synergy between Mn ABZI, nanovaccine, termed ONc-Mn-A-malF127, elevates levels interferon-β (IFNβ) 324- 8-fold vivo, compared use or ABZI alone. As such, activation cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-STING pathway induces sufficient dendritic cell (DC) maturation, eventually resulting death CD8+ T cell-sensitive tumors cell-resistant simultaneously promoting cytotoxic cells NK cells, respectively. Furthermore, with ONc used as chelator an efficient photosensitizer, photoinduced immunogenic (ICD) tumor releases damage-associated molecular patterns (DAMPs) neoantigens from dying primary upon laser irradiation, which are captured situ malF127 then transported DCs. After treatment, addition photothermal therapy, responses characterized level IFNβ further elevated another 4-fold. In murine cancer models, ICD-based metalloimmunotherapy using ONc-Mn-A-malF127 single dose intravenous injection achieved eradication distant tumors. Taken together, offers nanoplatform enhance efficacy ICD based strong abscopal effect.

Язык: Английский

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MnOOH-Catalyzed Autoxidation of Glutathione for Reactive Oxygen Species Production and Nanocatalytic Tumor Innate Immunotherapy

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(10), С. 5803 - 5815

Опубликована: Фев. 27, 2023

The antioxidant system, signed with reduced glutathione (GSH) overexpression, is the key weapon for tumor to resist attack by reactive oxygen species (ROS). Counteracting ROS depletion GSH an effective strategy guarantee antitumor efficacy of nanocatalytic therapy. However, simply reducing concentration does not sufficiently improve response therapy intervention. Herein, a well-dispersed MnOOH nanocatalyst developed catalyze autoxidation and peroxidase-like reaction concurrently respectively promote H2O2 decomposition produce abundant such as hydroxyl radical (·OH), thereby generating highly superadditive catalytic therapeutic efficacy. Such that transforms endogenous "antioxidant" into "oxidant" may open new avenue development medicine. Moreover, released Mn2+ can activate sensitize cGAS-STING pathway damaged intratumoral DNA double-strands induced produced further macrophage maturation M1-polarization, which will boost innate immunotherapeutic Resultantly, simple medicine capable simultaneously catalyzing generation, mediating immune activation, holds great potential in treatment malignant tumors.

Язык: Английский

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