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Tumor microenvironment-responsive Cu/CaO 2 nanocomposites for amplified pyroptosis and cuproptosis.

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Titel: Tumor microenvironment-responsive Cu/CaO 2 nanocomposites for amplified pyroptosis and cuproptosis.
Autoren: Li H; Department of Orthopedics Trauma and Microsurgery, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China; Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (MOE), Wuhan University, Wuhan 430072, China., Wang Y; Department of Orthopedics Trauma and Microsurgery, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China; Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (MOE), Wuhan University, Wuhan 430072, China., Liu Y; School of Chemistry and Materials Sciences, South-Central Minzu University, Wuhan 430074, China. Electronic address: yiliuchem@whu.edu.cn., Jiang P; Department of Orthopedics Trauma and Microsurgery, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China; Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (MOE), Wuhan University, Wuhan 430072, China. Electronic address: jiangpeng@whu.edu.cn.
Quelle: Journal of colloid and interface science [J Colloid Interface Sci] 2025 Nov 15; Vol. 698, pp. 138044. Date of Electronic Publication: 2025 Jun 02.
Publikationsart: Journal Article
Sprache: English
Info zur Zeitschrift: Publisher: Academic Press Country of Publication: United States NLM ID: 0043125 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1095-7103 (Electronic) Linking ISSN: 00219797 NLM ISO Abbreviation: J Colloid Interface Sci Subsets: MEDLINE
Imprint Name(s): Publication: Orlando, FL : Academic Press
Original Publication: New York.
MeSH-Schlagworte: Pyroptosis*/drug effects , Copper*/chemistry , Copper*/pharmacology , Tumor Microenvironment*/drug effects , Nanocomposites*/chemistry , Antineoplastic Agents*/pharmacology , Antineoplastic Agents*/chemistry , Oxides*/chemistry , Oxides*/pharmacology , Calcium Compounds*/chemistry , Calcium Compounds*/pharmacology, Animals ; Mice ; Humans ; Reactive Oxygen Species/metabolism ; Drug Screening Assays, Antitumor ; Photochemotherapy ; Mice, Inbred BALB C ; Particle Size ; Cell Proliferation/drug effects ; Photosensitizing Agents/pharmacology ; Photosensitizing Agents/chemistry ; Cell Line, Tumor ; Surface Properties ; Cell Survival/drug effects
Abstract: Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Pyroptosis and cuproptosis are promising strategies in cancer therapy. However, strategies to induce cell pyroptosis and cuproptosis are limited by the tumor microenvironment (TME). In this study, a multifunctional copper-based composite nanomaterial (CCS-ICG) was developed to enhance antitumor efficacy through a synergistic combination of chemodynamic therapy (CDT), photodynamic therapy (PDT), and photothermal therapy (PTT), alongside ion interference. This nanomaterial integrates endogenous and exogenous stimulation mechanisms to promote reactive oxygen species (ROS) production. Upon entering tumor cells, CCS-ICG decomposes to release H 2 O 2 and O 2 , effectively modulating the tumor microenvironment (TME) by elevating H 2 O 2 levels and alleviating hypoxia. Elevated H 2 O 2 enhances the Fenton-like activity of Cu 2+ , generating toxic OH and boosting CDT, while O 2 production improves PDT by promoting 1 O 2 generation. Additionally, intracellular accumulation of Cu 2+ induces cuproptosis, enhancing ROS generation and accumulation, while Ca 2+ release triggers calcium overload, amplifying oxidative stress. These mechanisms facilitate significant ROS generation, leading to pyroptosis, immunogenic cell death (ICD), and T cell infiltration, which collectively contribute to a potent antitumor immune response. In vivo and in vitro evaluations reveal that CCS-ICG effectively modulates the TME, exhibits superior antitumor activity, and displays favorable biocompatibility, highlighting its potential as a multimodal platform for synergistic cancer therapy.
(Copyright © 2025 Elsevier Inc. All rights reserved.)
Contributed Indexing: Keywords: Alongside ion interference; Chemodynamic therapy; Cuproptosis; Photodynamic therapy; Pyroptosis; Tumor microenvironment
Substance Nomenclature: 789U1901C5 (Copper)
0 (Antineoplastic Agents)
0 (Reactive Oxygen Species)
0 (Oxides)
0 (Calcium Compounds)
C7X2M0VVNH (lime)
0 (Photosensitizing Agents)
Entry Date(s): Date Created: 20250604 Date Completed: 20250715 Latest Revision: 20250715
Update Code: 20250715
DOI: 10.1016/j.jcis.2025.138044
PMID: 40466604
Datenbank: MEDLINE
Beschreibung
Abstract:Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br />Pyroptosis and cuproptosis are promising strategies in cancer therapy. However, strategies to induce cell pyroptosis and cuproptosis are limited by the tumor microenvironment (TME). In this study, a multifunctional copper-based composite nanomaterial (CCS-ICG) was developed to enhance antitumor efficacy through a synergistic combination of chemodynamic therapy (CDT), photodynamic therapy (PDT), and photothermal therapy (PTT), alongside ion interference. This nanomaterial integrates endogenous and exogenous stimulation mechanisms to promote reactive oxygen species (ROS) production. Upon entering tumor cells, CCS-ICG decomposes to release H <subscript>2</subscript> O <subscript>2</subscript> and O <subscript>2</subscript> , effectively modulating the tumor microenvironment (TME) by elevating H <subscript>2</subscript> O <subscript>2</subscript> levels and alleviating hypoxia. Elevated H <subscript>2</subscript> O <subscript>2</subscript> enhances the Fenton-like activity of Cu <sup>2+</sup> , generating toxic OH and boosting CDT, while O <subscript>2</subscript> production improves PDT by promoting <sup>1</sup> O <subscript>2</subscript> generation. Additionally, intracellular accumulation of Cu <sup>2+</sup> induces cuproptosis, enhancing ROS generation and accumulation, while Ca <sup>2+</sup> release triggers calcium overload, amplifying oxidative stress. These mechanisms facilitate significant ROS generation, leading to pyroptosis, immunogenic cell death (ICD), and T cell infiltration, which collectively contribute to a potent antitumor immune response. In vivo and in vitro evaluations reveal that CCS-ICG effectively modulates the TME, exhibits superior antitumor activity, and displays favorable biocompatibility, highlighting its potential as a multimodal platform for synergistic cancer therapy.<br /> (Copyright © 2025 Elsevier Inc. All rights reserved.)
ISSN:1095-7103
DOI:10.1016/j.jcis.2025.138044