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Nucleoside-Lipid-Based Nanoparticles for Phenazine Delivery: A New Therapeutic Strategy to Disrupt Hsp27-eIF4E Interaction in Castration Resistant Prostate Cancer ; Nucleoside-Lipid-Based Nanoparticles for Phenazine Delivery: A New Therapeutic Strategy to Disrupt Hsp27-eIF4E Interaction in Castration Resistant Prostate Cancer.

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  • Additional Information
    • Contributors:
      Centre de Recherche en Cancérologie de Marseille (CRCM); Aix Marseille Université (AMU)-Institut Paoli-Calmettes (IPC); Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS); Régulations Naturelles et Artificielles (ARNA); Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux Ségalen Bordeaux 2; Acides Nucléiques : Régulations Naturelle et Artificielle (ARNA); Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie - CNRS Chimie (INC-CNRS)-Centre National de la Recherche Scientifique (CNRS); Faculté des Sciences de Bizerte Université de Carthage; Université de Carthage (Tunisie) (UCAR); Centre Interdisciplinaire de Nanoscience de Marseille (CINaM); Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)
    • Publication Information:
      HAL CCSD
      MDPI
    • Publication Date:
      2021
    • Collection:
      Aix-Marseille Université: HAL
    • Abstract:
      International audience ; Heat shock protein 27 (Hsp27) has an established role in tumor progression and chemo-resistance of castration-resistant prostate cancer (CRPC). Hsp27 protects eukaryotic translation initiation factor 4E (eIF4E) from degradation, thereby maintaining survival during treatment. Phenazine derivative compound #14 was demonstrated to specifically disrupt Hsp27/eIF4E interaction and significantly delay castration-resistant tumor progression in prostate cancer xenografts. In the present work, various strategies of encapsulation of phenazine #14 with either DOTAU (N-[5′-(2′,3′-dioleoyl)uridine]-N′,N′,N′-trimethylammonium tosylate) and DOU-PEG2000 (5′-PEG2000-2′,3′-dioleoyluridine) nucleolipids (NLs) were developed in order to improve its solubilization, biological activity, and bioavailability. We observed that NLs-encapsulated phenazine #14-driven Hsp27-eIF4E interaction disruption increased cytotoxic effects on castration-resistant prostate cancer cell line and inhibited tumor growth in castration-resistant prostate cancer cell xenografted mice compared to phenazine #14 and NLs alone. Phenazine #14 NL encapsulation might represent an interesting nanostrategy for CRPC therapy.
    • Relation:
      info:eu-repo/semantics/altIdentifier/pmid/33925528; hal-03599172; https://hal.science/hal-03599172; https://hal.science/hal-03599172/document; https://hal.science/hal-03599172/file/pharmaceutics-13-00623.pdf; PUBMED: 33925528; PUBMEDCENTRAL: PMC8146835
    • Accession Number:
      10.3390/pharmaceutics13050623
    • Online Access:
      https://hal.science/hal-03599172
      https://hal.science/hal-03599172/document
      https://hal.science/hal-03599172/file/pharmaceutics-13-00623.pdf
      https://doi.org/10.3390/pharmaceutics13050623
    • Rights:
      info:eu-repo/semantics/OpenAccess
    • Accession Number:
      edsbas.26679EE0