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|a 10.1002/adma.202404784
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|a pubmed24n1563.xml
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|a eng
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|a Schneider, Paul
|e verfasserin
|4 aut
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|a Multicompartment Polyion Complex Micelles Based on Triblock Polypept(o)ides Mediate Efficient siRNA Delivery to Cancer-Associated Fibroblasts for Antistromal Therapy of Hepatocellular Carcinoma
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|c 2024
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|a Text
|b txt
|2 rdacontent
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|a ƒaComputermedien
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|2 rdamedia
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|a ƒa Online-Ressource
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|2 rdacarrier
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|a Date Completed 10.10.2024
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|a Date Revised 10.10.2024
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|a published: Print-Electronic
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|a Citation Status MEDLINE
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|a © 2024 The Author(s). Advanced Materials published by Wiley‐VCH GmbH.
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|a Hepatocellular carcinoma (HCC) is the most frequent type of primary liver cancer and the third leading cause for cancer-related death worldwide. The tumor is difficult-to-treat due to its inherent resistance to chemotherapy. Antistromal therapy is a novel therapeutic approach, targeting cancer-associated fibroblasts (CAF) in the tumor microenvironment. CAF-derived microfibrillar-associated protein 5 (MFAP-5) is identified as a novel target for antistromal therapy of HCC with high translational relevance. Biocompatible polypept(o)ide-based polyion complex micelles (PICMs) constructed with a triblock copolymer composed of a cationic poly(l-lysine) complexing anti-MFAP-5 siRNA (siMFAP-5) via electrostatic interaction, a poly(γ-benzyl-l-glutamate) block loading cationic amphiphilic drug desloratatine (DES) via π-π interaction as endosomal escape enhancer and polysarcosine poly(N-methylglycine) for introducing stealth properties, are generated for siRNA delivery. Intravenous injection of siMFAP-5/DES PICMs significantly reduces the hepatic tumor burden in a syngeneic implantation model of HCC, with a superior MFAP-5 knockdown effect over siMFAP-5 PICMs or lipid nanoparticles. Transcriptome and histological analysis reveal that MFAP-5 knockdown inhibited CAF-related tumor vascularization, suggesting the anti-angiogenic effect of RNA interference therapy. In conclusion, multicompartment PICMs combining siMFAP-5 and DES in a single polypept(o)ide micelle induce a specific knockdown of MFAP-5 and demonstrate a potent antitumor efficacy (80% reduced tumor burden vs untreated control) in a clinically relevant HCC model
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|a Journal Article
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|a desloratadine
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|a endosomal escape
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|a hepatocellular carcinoma
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|a polyion complex micelles
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|a polypept(o)ides
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|a siRNA co‐delivery
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|a RNA, Small Interfering
|2 NLM
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|a Micelles
|2 NLM
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|a Zhang, Heyang
|e verfasserin
|4 aut
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|a Simic, Leon
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|a Dai, Zhuqing
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|a Schrörs, Barbara
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|a Akilli-Öztürk, Özlem
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|a Lin, Jian
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|a Durak, Feyza
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|a Schunke, Jenny
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|a Bolduan, Vanessa
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|a Bogaert, Bram
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|a Schwiertz, David
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|a Schäfer, Gabriela
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|a Bros, Matthias
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|a Grabbe, Stephan
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|a Schattenberg, Jörn Markus
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|a Raemdonck, Koen
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|a Koynov, Kaloian
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|a Diken, Mustafa
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|a Kaps, Leonard
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|a Barz, Matthias
|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 36(2024), 41 vom: 05. Okt., Seite e2404784
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|x 1521-4095
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|g volume:36
|g year:2024
|g number:41
|g day:05
|g month:10
|g pages:e2404784
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|u http://dx.doi.org/10.1002/adma.202404784
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