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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Augmenting Immunogenic Cell Death and Alleviating Myeloid‐Derived Suppressor Cells by Sono‐Activatable Semiconducting Polymer Nanopartners for Immunotherapy

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

Опубликована: Май 11, 2023

Inducing immunogenic cell death (ICD) by sonodynamic therapy (SDT) is promising for cancer immunotherapy, which however inefficient due to oxygen depletion that compromises SDT effect and mediates recruitment of immunosuppressive myeloid-derived suppressor cells (MDSCs). The fabrication sono-activatable semiconducting polymer nanopartners (SPNTi ) simultaneously augment ICD alleviate MDSCs immunotherapy reported. A polymer, hydrophobic hypoxia-responsive tirapazamine (TPZ)-conjugate, MDSC-targeting drug (ibrutinib) are encapsulated inside such SPNTi with surface shell a singlet (1 O2 )-cleavable amphiphilic polymer. TPZ ibrutinib serve as partners enlarge immunotherapeutic effect. Upon sono-activation, generate 1 break -cleavable polymers in situ liberations TPZ-conjugate tumor sites, consumed create severe hypoxic microenvironment, which, activated augmenting action, while alleviates promoting antitumor immunological In bilateral mouse model, -mediated results growth restraints primary distant tumors noteworthy precaution metastases. This study thus provides strategy high precision safety via overcoming post-treatment hypoxia targeting MDSCs.

Язык: Английский

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Interrelation between Programmed Cell Death and Immunogenic Cell Death: Take Antitumor Nanodrug as an Example

Small Methods, Год журнала: 2023, Номер 7(5)

Опубликована: Янв. 27, 2023

Abstract Programmed cell death (PCD, mainly including apoptosis, necrosis, ferroptosis, pyroptosis, and autophagy) immunogenic (ICD), as important mechanisms, are widely reported in cancer therapy, understanding the relationship between two is significant for clinical tumor treatments. Considering that vast nanodrugs developed to induce PCD ICD simultaneously, this review, interrelationship described using nanomedicines examples. First, an overview of patterns focus on morphological differences interconnections among them provided. Then apoptosis terms endoplasmic reticulum stress by introducing various treatments recent developments with inducible immunogenicity. Next, crosstalk non‐apoptotic (including signaling pathways introduced their through examples further illustrated. Finally, its application prospects development new nanomaterials summarized. This review believed deepen ICD, extend biomedical applications nanodrugs, promote progress therapy.

Язык: Английский

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Stimulus Responsive Nanocarrier for Enhanced Antitumor Responses Against Hepatocellular Carcinoma

International Journal of Nanomedicine, Год журнала: 2024, Номер Volume 19, С. 13339 - 13355

Опубликована: Дек. 1, 2024

Hepatocellular carcinoma (HCC) is a serious global health concern, accounting for about 90% of all liver cancer instances. Surgical treatment fundamental aspect HCC management; however, the challenge postoperative recurrence significantly impacts mortality rates.

Язык: Английский

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Oxygen‐carrying semiconducting polymer nanoprodrugs induce sono‐pyroptosis for deep‐tissue tumor treatment

Exploration, Год журнала: 2024, Номер 4(4)

Опубликована: Фев. 19, 2024

Abstract Sonodynamic therapy (SDT) has been explored for cancer therapy, especially deep tumors due to its low tissue penetration restriction. The therapeutic efficacy of SDT is limited the complicated tumor microenvironment. This study reports construction oxygen‐carrying semiconducting polymer nanoprodrugs (OSPN pro ) treatment via combining amplified with pyroptosis. An oxygen carrier perfluorohexane, sonodynamic as sonosensitizer, and reactive species (ROS)‐responsive prodrug are co‐loaded into a nanoparticle system, leading formation these nanoprodrugs. Such OSPN show an effective accumulation in tissues after systemic administration, which they deliver relieve hypoxia microenvironment thus mediate producing ROS under ultrasound (US) irradiation, even when covered 2‐cm chicken breast tissue. In addition, ROS‐responsive prodrugs activated by generated trigger pyroptosis cells. sono‐pyroptosis induces strong antitumor immunity obviously higher level infiltrations effector immune cells tumors. Therefore, ‐based combinational can greatly inhibit growth tissue‐covered suppress metastasis. offers nanoplatform strategy.

Язык: Английский

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Nanotechnology Reprogramming Metabolism for Enhanced Tumor Immunotherapy

ACS Nano, Год журнала: 2024, Номер 18(3), С. 1846 - 1864

Опубликована: Янв. 5, 2024

Mutation burden, hypoxia, and immunoediting contribute to altered metabolic profiles in tumor cells, resulting a microenvironment (TME) characterized by accumulation of toxic metabolites depletion various nutrients, which significantly hinder the antitumor immunity via multiple mechanisms, hindering efficacy immunotherapies. In-depth investigation mechanisms underlying these phenomena are vital for developing effective drugs therapies, while therapeutic effects metabolism-targeting restricted off-target toxicity toward effector immune cells high dosage-mediated side effects. Nanotechnologies, exhibit versatility plasticity targeted delivery metabolism modulation, have been widely applied boost immunometabolic therapies strategies, including targeting pathways. In this review, recent advances understanding roles cell both immunoevasion immunosuppression reviewed, nanotechnology-based reprogramming strategies enhanced immunotherapies discussed.

Язык: Английский

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Leveraging Semiconducting Polymer Nanoparticles for Combination Cancer Immunotherapy

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

Опубликована: Окт. 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.

Язык: Английский

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Second near-infrared light-activated semiconducting polymer nanomediators enable three-in-one tumor microenvironment modulation for combination immunotherapy

Nano Today, Год журнала: 2023, Номер 50, С. 101833 - 101833

Опубликована: Март 25, 2023

Язык: Английский

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Cell Death Pathway Regulation by Functional Nanomedicines for Robust Antitumor Immunity

Advanced Science, Год журнала: 2023, Номер 11(3)

Опубликована: Ноя. 20, 2023

Abstract Cancer immunotherapy has become a mainstream cancer treatment over traditional therapeutic modes. cells can undergo programmed cell death including ferroptosis, pyroptosis, autophagy, necroptosis, apoptosis and cuproptosis which are find to have intrinsic relationships with host antitumor immune response. However, direct use of inducers or regulators may bring about severe side effects that also be rapidly excreted degraded low efficacy. Nanomaterials able carry them for long circulation time, high tumor accumulation controlled release achieve satisfactory effect. Nowadays, large number studies focused on nanomedicines‐based strategies through modulating modalities potentiate immunity. Herein, types their function first summarized, state‐of‐the‐art research progresses in nanomedicines mediated pathways (e.g., cuproptosis) response provocation highlighted. Subsequently, the conclusion outlook potential focus discussed.

Язык: Английский

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In Situ Redox of TiSe₂ Nanoplates to Excite Chemodynamic‐Enhanced Cancer Sono‐Immunotherapy

Small Structures, Год журнала: 2024, Номер 5(6)

Опубликована: Фев. 22, 2024

Different from the direct delivery of chemodynamic agents into tumor tissue for therapy (CDT), this work reports fabrication heterojunction sonosensitizers (CD/TiSe 2 ) in situ generation by responding to microenvironment (TME), realizing CDT‐enhanced sono‐immunotherapy. The redox TiSe acidic TME leads formation TiO x Se 2− containing (0), selenate, and Ti 3+ /Ti 4+ couple, which can facilitate CDT through a ‐mediated Fenton‐like reaction consume overexpressed glutathione (GSH) via GSH depletion. Moreover, ions generated process promote maturation dendritic cells, consequently activating adaptive immune responses. In another aspect, construction heterojunctions within carbon dots improves reactive oxygen species (ROS) efficiency cascaded manner, enhances sonodynamic activity amplifies performance. More importantly, ROS produced efficiently triggers immunogenic cell death synergistic based on elicitation antitumor immunity with aid an checkpoint blockade. This thus provides distinct paradigm transition metal selenide‐originated agent

Язык: Английский

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