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Title:
Zinc-copper bimetallic nanoplatforms trigger photothermal-amplified cuproptosis and cGAS-STING activation for enhancing triple-negative breast cancer immunotherapy | Journal of Nanobiotechnology
Description:
Triple-negative breast cancer (TNBC) is characterized by high rates of metastasis and recurrence, along with a low sensitivity to immunotherapy, resulting in a paucity of effective therapeutic strategies. Herein, we have developed polydopamine-coated zinc-copper bimetallic nanoplatforms (Cu-ZnO2@PDA nanoplatforms, abbreviated CZP NPs) that can efficiently induce photothermal amplified cuproptosis and cGAS-STING signaling pathway activation, thereby reversing the immunosuppressive tumor microenvironment of TNBC, upregulating PD-L1 expression, and boosting the efficacy of anti-programmed death-ligand 1 antibody (αPD-L1)-based immunotherapy. Within the acidic tumor microenvironment (TME), CZP NPs spontaneously release copper and zinc ions and hydrogen peroxide, generating highly oxidative hydroxyl radicals and downregulating iron-sulfur cluster proteins. These actions lead to the disruption of mitochondrial integrity, the release of mitochondrial DNA (mtDNA) and irreversible cuproptosis. The further synergy between mtDNA and zinc ions potentiates the activation of the cGAS-STING signaling pathway, triggering a robust antitumor immune response and sensitizing TNBC to αPD-L1 therapy. Additionally, using an 808 nm near-infrared laser for photothermal therapy significantly augments these effects, resulting in a cascade amplification of therapeutic efficacy against TNBC. The strategic combination of CZP NPs with αPD-L1 markedly bolsters antitumor immunity and suppresses tumor growth. Collectively, our findings present a promising synergistic strategy for TNBC treatment by linking cuproptosis, cGAS-STING activation, photothermal therapy, and immunotherapy. Graphical abstract
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Keywords {🔍}
czp, nps, fig, cells, pubmed, tumor, nir, article, google, scholar, cancer, treatment, cas, control, cuproptosis, copper, mice, cgassting, pathway, expression, release, immune, analysis, group, activation, immunotherapy, ions, groups, tnbc, antitumor, αpdl, therapy, breast, photothermal, signaling, results, central, significant, cell, zno, treatments, pdl, mitochondrial, levels, zinc, mtdna, significantly, treated, dcs, wang,
Topics {✒️}
combinatorial czp + nir + αpd-l1 strategy triple-negative breast cancer czp + nir + αpd-l1 treatment resulted flow cytometric profiles cytokine-cytokine receptor interaction high-performance ferroptosis therapy article download pdf energy dispersive x-ray cgas-sting signaling pathway czp + nir + αpd-l1 showed nf-κb signaling pathway cgas-sting pathway stimulation d-luciferin potassium salt czp + nir + αpd-l1 group consecutive heating-cooling cycles prevent taxane-induced pyroptosis tumor-draining lymph nodes il-17 signaling pathway concentration-dependent temperature-time curves promotes nuclear factor-κb cyclic gmp-amp synthase combined czp + nir therapy full access mtdna-cgas-sting signaling αpd-l1 significantly reshapes small-cell lung cancer cgas-sting signal transduction czp + nir treatment resulted elevating pd-l1 levels transform ici-unresponsive tumors receptor signaling pathway copper-mediated therapies average pd-l1 expression photothermal performance exhibited ici-based immunotherapy [27 czp + nir therapy resulting tumor immune microenvironment therapeutic effects mediated inhibiting nf-κb activation 100µg/ml czp nps article zhou upregulate pd-l1 expression adaptive immune responses metal ions czp + nir group relative czp + nir treatment compared czp + nir treatment increased similar ici-sensitizing effect triggers nf-κb activation cgas-sting pathway
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headline:Zinc-copper bimetallic nanoplatforms trigger photothermal-amplified cuproptosis and cGAS-STING activation for enhancing triple-negative breast cancer immunotherapy
description:Triple-negative breast cancer (TNBC) is characterized by high rates of metastasis and recurrence, along with a low sensitivity to immunotherapy, resulting in a paucity of effective therapeutic strategies. Herein, we have developed polydopamine-coated zinc-copper bimetallic nanoplatforms (Cu-ZnO2@PDA nanoplatforms, abbreviated CZP NPs) that can efficiently induce photothermal amplified cuproptosis and cGAS-STING signaling pathway activation, thereby reversing the immunosuppressive tumor microenvironment of TNBC, upregulating PD-L1 expression, and boosting the efficacy of anti-programmed death-ligand 1 antibody (αPD-L1)-based immunotherapy. Within the acidic tumor microenvironment (TME), CZP NPs spontaneously release copper and zinc ions and hydrogen peroxide, generating highly oxidative hydroxyl radicals and downregulating iron-sulfur cluster proteins. These actions lead to the disruption of mitochondrial integrity, the release of mitochondrial DNA (mtDNA) and irreversible cuproptosis. The further synergy between mtDNA and zinc ions potentiates the activation of the cGAS-STING signaling pathway, triggering a robust antitumor immune response and sensitizing TNBC to αPD-L1 therapy. Additionally, using an 808 nm near-infrared laser for photothermal therapy significantly augments these effects, resulting in a cascade amplification of therapeutic efficacy against TNBC. The strategic combination of CZP NPs with αPD-L1 markedly bolsters antitumor immunity and suppresses tumor growth. Collectively, our findings present a promising synergistic strategy for TNBC treatment by linking cuproptosis, cGAS-STING activation, photothermal therapy, and immunotherapy.
datePublished:2025-02-24T00:00:00Z
dateModified:2025-02-24T00:00:00Z
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keywords:
Triple-negative breast cancer
Immunotherapy
Cuproptosis
cGAS-STING signaling pathway
Photothermal therapy
Biotechnology
Nanotechnology
Molecular Medicine
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headline:Zinc-copper bimetallic nanoplatforms trigger photothermal-amplified cuproptosis and cGAS-STING activation for enhancing triple-negative breast cancer immunotherapy
description:Triple-negative breast cancer (TNBC) is characterized by high rates of metastasis and recurrence, along with a low sensitivity to immunotherapy, resulting in a paucity of effective therapeutic strategies. Herein, we have developed polydopamine-coated zinc-copper bimetallic nanoplatforms (Cu-ZnO2@PDA nanoplatforms, abbreviated CZP NPs) that can efficiently induce photothermal amplified cuproptosis and cGAS-STING signaling pathway activation, thereby reversing the immunosuppressive tumor microenvironment of TNBC, upregulating PD-L1 expression, and boosting the efficacy of anti-programmed death-ligand 1 antibody (αPD-L1)-based immunotherapy. Within the acidic tumor microenvironment (TME), CZP NPs spontaneously release copper and zinc ions and hydrogen peroxide, generating highly oxidative hydroxyl radicals and downregulating iron-sulfur cluster proteins. These actions lead to the disruption of mitochondrial integrity, the release of mitochondrial DNA (mtDNA) and irreversible cuproptosis. The further synergy between mtDNA and zinc ions potentiates the activation of the cGAS-STING signaling pathway, triggering a robust antitumor immune response and sensitizing TNBC to αPD-L1 therapy. Additionally, using an 808 nm near-infrared laser for photothermal therapy significantly augments these effects, resulting in a cascade amplification of therapeutic efficacy against TNBC. The strategic combination of CZP NPs with αPD-L1 markedly bolsters antitumor immunity and suppresses tumor growth. Collectively, our findings present a promising synergistic strategy for TNBC treatment by linking cuproptosis, cGAS-STING activation, photothermal therapy, and immunotherapy.
datePublished:2025-02-24T00:00:00Z
dateModified:2025-02-24T00:00:00Z
pageStart:1
pageEnd:19
license:http://creativecommons.org/licenses/by-nc-nd/4.0/
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keywords:
Triple-negative breast cancer
Immunotherapy
Cuproptosis
cGAS-STING signaling pathway
Photothermal therapy
Biotechnology
Nanotechnology
Molecular Medicine
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