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231226s2023 xx |||||o 00| ||eng c |
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|a 10.1002/adma.202207733
|2 doi
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|a pubmed25n1186.xml
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|a eng
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| 100 |
1 |
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|a Sun, Jiali
|e verfasserin
|4 aut
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| 245 |
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|a Azide-Masked Resiquimod Activated by Hypoxia for Selective Tumor Therapy
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|c 2023
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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
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|a Date Completed 21.07.2023
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|a Date Revised 21.07.2023
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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 Resiquimod (R848) is an immunomodulator that causes a severe systemic inflammatory reaction due to low tumor selectivity, thus hindering its use in cancer therapy. Therefore, an azide-masked prodrug (R848-N3 ) of R848 is developed, which is selectively activated to R848 in hypoxic tumors. R848-N3 significantly reduces pro-inflammatory cytokines in treated mice to 1/12 compared to R848 at the same dose. In addition, combretastatin A4 nanoparticles (CA4-NPs) are used to enhance the tumor selectivity of R848-N3 by elevating the level of tumor hypoxia. R848-N3 +CA4-NPs has higher tumor selectivity than the intratumoral injection of R848 at 1 h after administration. The concentration of the active R848 in the tumor is 21.45-fold that in the heart. Benefiting from the high tumor selectivity of R848-N3 , R848-N3 +CA4-NPs+anti-PD1 exerted 94.1% tumor suppression and 40.0% tumor cure. Therefore, this work highlights the potential of azide-masking strategy in the development of tumor-selective prodrugs with reduced toxicity
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|a Journal Article
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|a azide-masked
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|a hypoxia activated
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|a resiquimod (R848)
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|a selective therapy
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| 650 |
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|a resiquimod
|2 NLM
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| 650 |
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|a V3DMU7PVXF
|2 NLM
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| 650 |
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|a Azides
|2 NLM
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| 650 |
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7 |
|a Imidazoles
|2 NLM
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| 650 |
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|a Prodrugs
|2 NLM
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| 700 |
1 |
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|a Liu, Zhilin
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Yao, Haochen
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Zhang, Honglei
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Zheng, Mengfei
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Shen, Na
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Cheng, Jianjun
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Tang, Zhaohui
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Chen, Xuesi
|e verfasserin
|4 aut
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| 773 |
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|i Enthalten in
|t Advanced materials (Deerfield Beach, Fla.)
|d 1998
|g 35(2023), 29 vom: 03. Juli, Seite e2207733
|w (DE-627)NLM098206397
|x 1521-4095
|7 nnas
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|g volume:35
|g year:2023
|g number:29
|g day:03
|g month:07
|g pages:e2207733
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|u http://dx.doi.org/10.1002/adma.202207733
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