Chemotherapy Mediated by Biomimetic Polymeric Nanoparticles Potentiates Enhanced Tumor Immunotherapy via Amplification of Endoplasmic Reticulum Stress and Mitochondrial Dysfunction - Archive ouverte HAL Access content directly
Journal Articles Advanced Materials Year : 2022

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

Abstract

Construction of multifunctional nanoplatforms to elevate chemotherapeutic efficacy and induce long-term antitumor immunity still remains to be an extreme challenge. Herein, we report the design of an advanced redox-responsive nanomedicine formulation based on phosphorus dendrimer-copper(II) complexes (1G3-Cu)- and toyocamycin (Toy)-loaded polymeric nanoparticles (GCT NPs) coated with cancer cell membranes (CM). The designed GCT@CM NPs with a size of 210 nm are stable under a physiological condition but are rapidly dissociated in the reductive tumor microenvironment to deplete glutathione and release drugs. The co-loading of 1G3-Cu and Toy within the NPs causes significant tumor cell apoptosis and immunogenic cell death through 1G3-Cu-induced mitochondrial dysfunction and Toy-mediated amplification of endoplasmic reticulum stress, respectively, thus effectively suppressing tumor growth, promoting dendritic cell maturation, and increasing tumor-infiltrating cytotoxic T lymphocytes. Likewise, the coated CM and the loaded 1G3-Cu render the GCT@CM NPs with homotypic targeting and T1-weighted magnetic resonance imaging of tumors, respectively. With the assistance of programmed cell death ligand 1 antibody, the GCT@CM NP-mediated chemotherapy can significantly potentiate tumor immunotherapy for effective inhibition of tumor recurrence and metastasis. The developed GCT@CM NPs hold a great potential for chemotherapy-potentiated immunotherapy of different tumor types through different mechanisms or synergies.
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Dates and versions

hal-03807818 , version 1 (10-10-2022)

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Yunqi Guo, Yu Fan, Zhiqiang Wang, Gaoming Li, Mengsi Zhan, et al.. Chemotherapy Mediated by Biomimetic Polymeric Nanoparticles Potentiates Enhanced Tumor Immunotherapy via Amplification of Endoplasmic Reticulum Stress and Mitochondrial Dysfunction. Advanced Materials, 2022, 34 (42), pp.2206861. ⟨10.1002/adma.202206861⟩. ⟨hal-03807818⟩
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