Chemotherapy Mediated by Biomimetic Polymeric Nanoparticles Potentiates Enhanced Tumor Immunotherapy via Amplification of Endoplasmic Reticulum Stress and Mitochondrial Dysfunction

Yunqi Guo; Yu Fan; Zhiqiang WangGaoming LiMengsi ZhanJunli GongJean-Pierre MajoralXiangyang ShiMingwu Shen

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Chemotherapy Mediated by Biomimetic Polymeric Nanoparticles Potentiates Enhanced Tumor Immunotherapy via Amplification of Endoplasmic Reticulum Stress and Mitochondrial Dysfunction

机译：Chemotherapy Mediated by Biomimetic Polymeric Nanoparticles Potentiates Enhanced Tumor Immunotherapy via Amplification of Endoplasmic Reticulum Stress and Mitochondrial Dysfunction

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Construction of multifunctional nanoplatforms to elevate chemotherapeuticefficacy and induce long-term antitumor immunity still remains to be anextreme challenge. Herein, the design of an advanced redox-responsivenanomedicine formulation based on phosphorus dendrimer–copper(II)complexes (1G3-Cu)- and toyocamycin (Toy)-loaded polymeric nanoparticles(GCT NPs) coated with cancer cell membranes (CM) are reported. Thedesigned GCT@CM NPs with a size of 210 nm are stable under physiologicalconditions but are rapidly dissociated in the reductive tumor microenvironmentto deplete glutathione and release drugs. The co-loading of 1G3-Cuand Toy within the NPs causes significant tumor cell apoptosis and immunogeniccell death through 1G3-Cu-induced mitochondrial dysfunction andToy-mediated amplification of endoplasmic reticulum stress, respectively,thus effectively suppressing tumor growth, promoting dendritic cell maturation,and increasing tumor-infiltrating cytotoxic T lymphocytes. Likewise, thecoated CM and the loaded 1G3-Cu render the GCT@CM NPs with homotypictargeting and T1-weighted magnetic resonance imaging of tumors, respectively.With the assistance of programmed cell death ligand 1 antibody, theGCT@CM NP-mediated chemotherapy can significantly potentiate tumorimmunotherapy for effective inhibition of tumor recurrence and metastasis.The developed GCT@CM NPs hold a great potential for chemotherapy-potentiatedimmunotherapy of different tumor types through different mechanismsor synergies.

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来源
《Advanced Materials》 |2022年第47期|2206861.1-2206861.18|共18页
作者
Yunqi Guo; Yu Fan; Zhiqiang WangGaoming LiMengsi ZhanJunli GongJean-Pierre MajoralXiangyang ShiMingwu Shen;
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State Key Laboratory for Modification of Chemical Fibers and PolymerMaterialsShanghai Engineering Research Center of Nano-Biomaterialsand Regenerative MedicineCollege of Biological Science and Medical EngineeringDonghua UniversityShanghai 201620, P. R. Ch;

Laboratoire de Chimie de Coordination du CNRSToulouse 31077, France;

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正文语种英语
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chemotherapy-potentiated immunotherapy; immunogenic cell death; phosphorus dendrimers; redox-responsiveness; toyocamycin;

Chemotherapy Mediated by Biomimetic Polymeric Nanoparticles Potentiates Enhanced Tumor Immunotherapy via Amplification of Endoplasmic Reticulum Stress and Mitochondrial Dysfunction

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