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20240315232943.0 |
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231226s2024 xx |||||o 00| ||eng c |
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|a 10.1002/adma.202310456
|2 doi
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|a pubmed24n1330.xml
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|a (DE-627)NLM365827118
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|a (NLM)38092007
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|a DE-627
|b ger
|c DE-627
|e rakwb
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|a eng
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| 100 |
1 |
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|a Yu, Bingzheng
|e verfasserin
|4 aut
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1 |
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|a Platinum Prodrug Nanoparticles with COX-2 Inhibition Amplify Pyroptosis for Enhanced Chemotherapy and Immune Activation of Pancreatic Cancer
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|c 2024
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|a Text
|b txt
|2 rdacontent
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|a ƒaComputermedien
|b c
|2 rdamedia
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|a ƒa Online-Ressource
|b cr
|2 rdacarrier
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|a Date Completed 15.03.2024
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|a Date Revised 15.03.2024
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|a published: Print-Electronic
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|a Citation Status MEDLINE
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|a © 2023 Wiley-VCH GmbH.
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|a Pyroptosis, an emerging mechanism of programmed cell death, holds great potential to trigger a robust antitumor immune response. Platinum-based chemotherapeutic agents can induce pyroptosis via caspase-3 activation. However, these agents also enhance cyclooxygenase-2 (COX-2) expression in tumor tissues, leading to drug resistance and immune evasion in pancreatic cancer and significantly limiting the effectiveness of chemotherapy-induced pyroptosis. Here, an amphiphilic polymer (denoted as PHDT-Pt-In) containing both indomethacin (In, a COX-2 inhibitor) and platinum(IV) prodrug (Pt(IV)) is developed, which is responsive to glutathione (GSH). This polymer self-assemble into nanoparticles (denoted as Pt-In NP) that can disintegrate in cancer cells due to the GSH responsiveness, releasing In to inhibit the COX-2 expression, hence overcoming the chemoresistance and amplifying cisplatin-induced pyroptosis. In a pancreatic cancer mouse model, Pt-In NP significantly inhibit tumor growth and elicit both innate and adaptive immune responses. Moreover, when combined with anti-programmed death ligand (α-PD-L1) treatment, Pt-In NP demonstrate the ability to completely suppress metastatic tumors, transforming "cold tumors" into "hot tumors". Overall, the sustained release of Pt(IV) and In from Pt-In NP amplifies platinum-drug-induced pyroptosis to elicit long-term immune responses, hence presenting a generalizable strategy for pancreatic cancer
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|a Journal Article
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|a chemotherapy
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|a cyclooxygenase 2
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|a immunotherapy
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|a platinum drug
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|a pyroptosis
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|a Prodrugs
|2 NLM
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|a Platinum
|2 NLM
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| 650 |
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|a 49DFR088MY
|2 NLM
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| 650 |
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|a Cyclooxygenase 2
|2 NLM
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| 650 |
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|a EC 1.14.99.1
|2 NLM
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| 650 |
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|a Cisplatin
|2 NLM
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| 650 |
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|a Q20Q21Q62J
|2 NLM
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| 650 |
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|a Polymers
|2 NLM
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| 700 |
1 |
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|a Wang, Yushu
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Bing, Tiejun
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Tang, Yujing
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Huang, Jia
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Xiao, Haihua
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Liu, Chaoyong
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Yu, Yingjie
|e verfasserin
|4 aut
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| 773 |
0 |
8 |
|i Enthalten in
|t Advanced materials (Deerfield Beach, Fla.)
|d 1998
|g 36(2024), 11 vom: 13. März, Seite e2310456
|w (DE-627)NLM098206397
|x 1521-4095
|7 nnns
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| 773 |
1 |
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|g volume:36
|g year:2024
|g number:11
|g day:13
|g month:03
|g pages:e2310456
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| 856 |
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|u http://dx.doi.org/10.1002/adma.202310456
|3 Volltext
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