@article{01JPSQPDH5JQ87VJQFSEZS362B,
  abstract     = {{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(gamma-benzyl-l-glutamate) block loading cationic amphiphilic drug desloratatine (DES) via pi-pi 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.}},
  author       = {{Schneider, Paul and Zhang, Heyang and Simic, Leon and Dai, Zhuqing and Schrörs, Barbara and Akilli‐Öztürk, Özlem and Lin, Jian and Durak, Feyza and Schunke, Jenny and Bolduan, Vanessa and Bogaert, Bram and Schwiertz, David and Schäfer, Gabriela and Bros, Matthias and Grabbe, Stephan and Schattenberg, Jörn Markus and Raemdonck, Koen and Koynov, Kaloian and Diken, Mustafa and Kaps, Leonard and Barz, Matthias}},
  issn         = {{0935-9648}},
  journal      = {{ADVANCED MATERIALS}},
  keywords     = {{hepatocellular carcinoma,polyion complex micelles,polypept(o)ides,siRNA co-delivery,desloratadine,endosomal escape,COPOLYMERS SYNTHESIS,ENDOSOMAL ESCAPE,COPOLYPEPT(O)IDES,POLYSARCOSINE,POLYPLEX,CELLS,LIVER,MFAP5}},
  language     = {{eng}},
  number       = {{41}},
  title        = {{Multicompartment polyion complex micelles based on triblock polypept(o)ides mediate efficient siRNA delivery to cancer‐associated fibroblasts for antistromal therapy of hepatocellular carcinoma}},
  url          = {{http://doi.org/10.1002/adma.202404784}},
  volume       = {{36}},
  year         = {{2024}},
}

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