Photothermally Triggered Copper Payload Release for Cuproptosis‐Promoted Cancer Synergistic Therapy

Cuproptosis is a new form of programmed cell death and exhibits enormous potential in cancer treatment. However, reducing the undesirable Cu ion release in normal tissue and maximizing the copper‐induced therapeutic effect in cancer sites are two main challenges. In this study, we constructed a phot...

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Published inAngewandte Chemie Vol. 135; no. 12
Main Authors Zhou, Jie, Yu, Qiao, Song, Juan, Li, Shan, Li, Xiang‐Ling, Kang, Bin K., Chen, Hong‐Yuan, Xu, Jing‐Juan
Format Journal Article
LanguageEnglish
Published Weinheim Wiley Subscription Services, Inc 13.03.2023
Subjects
Apoptosis
Cancer
Cell death
Chemistry
Copper
Copper Delivery
Cuproptosis
Cytotoxicity
Disulfiram
Gold
Growth inhibition
Mitochondria
Nanostructures
Photothermally Triggered Release
Protein interaction
Synergistic Therapy
Therapy
Tumor cells
Tumors
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Abstract Cuproptosis is a new form of programmed cell death and exhibits enormous potential in cancer treatment. However, reducing the undesirable Cu ion release in normal tissue and maximizing the copper‐induced therapeutic effect in cancer sites are two main challenges. In this study, we constructed a photothermally triggered nanoplatform (Au@MSN‐Cu/PEG/DSF) to realize on‐demand delivery for synergistic therapy. The released disulfiram (DSF) chelated with Cu2+ in situ to generate highly cytotoxic bis(diethyldithiocarbamate)copper (CuET), causing cell apoptosis, and the formed Cu+ species promoted toxic mitochondrial protein aggregation, leading to cell cuproptosis. Synergistic with photothermal therapy, Au@MSN‐Cu/PEG/DSF could effectively kill tumor cells and inhibit tumor growth (inhibition rate up to 80.1 %). These results provide a promising perspective for potential cancer treatment based on cuproptosis, and may also inspire the design of advanced nano‐therapeutic platforms. A gold‐nanorod‐based, copper‐doped, and disulfiram (DSF)‐loaded multifunctional therapeutic nanoplatform (Au@MSN‐Cu/PEG/DSF) was fabricated to deliver DSF and Cu2+ into cancer cells efficiently. A photothermal effect triggered on‐command payload release remotely to form cytotoxic bis(diethyldithiocarbamate)copper (CuET) and Cu+ in situ. This cuproptosis‐based strategy offers synergistic therapeutic modalities.
AbstractList Cuproptosis is a new form of programmed cell death and exhibits enormous potential in cancer treatment. However, reducing the undesirable Cu ion release in normal tissue and maximizing the copper‐induced therapeutic effect in cancer sites are two main challenges. In this study, we constructed a photothermally triggered nanoplatform (Au@MSN‐Cu/PEG/DSF) to realize on‐demand delivery for synergistic therapy. The released disulfiram (DSF) chelated with Cu 2+ in situ to generate highly cytotoxic bis(diethyldithiocarbamate)copper (CuET), causing cell apoptosis, and the formed Cu + species promoted toxic mitochondrial protein aggregation, leading to cell cuproptosis. Synergistic with photothermal therapy, Au@MSN‐Cu/PEG/DSF could effectively kill tumor cells and inhibit tumor growth (inhibition rate up to 80.1 %). These results provide a promising perspective for potential cancer treatment based on cuproptosis, and may also inspire the design of advanced nano‐therapeutic platforms.
Cuproptosis is a new form of programmed cell death and exhibits enormous potential in cancer treatment. However, reducing the undesirable Cu ion release in normal tissue and maximizing the copper‐induced therapeutic effect in cancer sites are two main challenges. In this study, we constructed a photothermally triggered nanoplatform (Au@MSN‐Cu/PEG/DSF) to realize on‐demand delivery for synergistic therapy. The released disulfiram (DSF) chelated with Cu2+ in situ to generate highly cytotoxic bis(diethyldithiocarbamate)copper (CuET), causing cell apoptosis, and the formed Cu+ species promoted toxic mitochondrial protein aggregation, leading to cell cuproptosis. Synergistic with photothermal therapy, Au@MSN‐Cu/PEG/DSF could effectively kill tumor cells and inhibit tumor growth (inhibition rate up to 80.1 %). These results provide a promising perspective for potential cancer treatment based on cuproptosis, and may also inspire the design of advanced nano‐therapeutic platforms.
Cuproptosis is a new form of programmed cell death and exhibits enormous potential in cancer treatment. However, reducing the undesirable Cu ion release in normal tissue and maximizing the copper‐induced therapeutic effect in cancer sites are two main challenges. In this study, we constructed a photothermally triggered nanoplatform (Au@MSN‐Cu/PEG/DSF) to realize on‐demand delivery for synergistic therapy. The released disulfiram (DSF) chelated with Cu2+ in situ to generate highly cytotoxic bis(diethyldithiocarbamate)copper (CuET), causing cell apoptosis, and the formed Cu+ species promoted toxic mitochondrial protein aggregation, leading to cell cuproptosis. Synergistic with photothermal therapy, Au@MSN‐Cu/PEG/DSF could effectively kill tumor cells and inhibit tumor growth (inhibition rate up to 80.1 %). These results provide a promising perspective for potential cancer treatment based on cuproptosis, and may also inspire the design of advanced nano‐therapeutic platforms. A gold‐nanorod‐based, copper‐doped, and disulfiram (DSF)‐loaded multifunctional therapeutic nanoplatform (Au@MSN‐Cu/PEG/DSF) was fabricated to deliver DSF and Cu2+ into cancer cells efficiently. A photothermal effect triggered on‐command payload release remotely to form cytotoxic bis(diethyldithiocarbamate)copper (CuET) and Cu+ in situ. This cuproptosis‐based strategy offers synergistic therapeutic modalities.
Author Kang, Bin K.
Zhou, Jie
Li, Xiang‐Ling
Li, Shan
Yu, Qiao
Song, Juan
Chen, Hong‐Yuan
Xu, Jing‐Juan
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CitedBy_id crossref_primary_10_1021_jacs_3c08622
crossref_primary_10_1016_j_actbio_2023_04_003
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Snippet Cuproptosis is a new form of programmed cell death and exhibits enormous potential in cancer treatment. However, reducing the undesirable Cu ion release in...
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SubjectTerms Apoptosis
Cancer
Cell death
Chemistry
Copper
Copper Delivery
Cuproptosis
Cytotoxicity
Disulfiram
Gold
Growth inhibition
Mitochondria
Nanostructures
Photothermally Triggered Release
Protein interaction
Synergistic Therapy
Therapy
Tumor cells
Tumors
Title Photothermally Triggered Copper Payload Release for Cuproptosis‐Promoted Cancer Synergistic Therapy
URI https://onlinelibrary.wiley.com/doi/abs/10.1002%2Fange.202213922
https://www.proquest.com/docview/2782883042
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