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Article

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

1
Centre de Recherche en Cancérologie de Marseille, CRCM, Inserm UMR 1068, CNRS, UMR 7258, Aix-Marseille University U105, Institut Paoli-Calmettes, F-13009 Marseille, France
2
Unit of Immunology Microbiology Environmental and Carcinogenesis (IMEC), Science Faculty of Bizerte, University of Carthage, 7000 Bizerte, Tunisia
3
ARNA Laboratory, INSERM U1212/CNRS, UMR 5320, University of Bordeaux, F-33076 Bordeaux, France
4
Biophysics and Nuclear Medicine Department, La Timone University Hospital, European Center for Research in Medical Imaging, Aix-Marseille University, F-13005 Marseille, France
5
Centre Interdisciplinaire de Nanoscience de Marseille, Aix-Marseille University, CNRS, UMR 7325, 163, Avenue de Luminy, F-13288 Marseille, France
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this paper.
Academic Editor: Donato Cosco
Pharmaceutics 2021, 13(5), 623; https://doi.org/10.3390/pharmaceutics13050623
Received: 10 February 2021 / Revised: 12 April 2021 / Accepted: 13 April 2021 / Published: 27 April 2021
(This article belongs to the Special Issue Cancer Nanomedicine—From the Bench to the Bedside)
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. View Full-Text
Keywords: nucleolipid; dialkoxyphenazine; nanoformulation; prostate cancer nucleolipid; dialkoxyphenazine; nanoformulation; prostate cancer
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MDPI and ACS Style

Ziouziou, H.; Paris, C.; Benizri, S.; Le, T.K.; Andrieu, C.; Nguyen, D.T.; Appavoo, A.; Taïeb, D.; Brunel, F.; Oueslati, R.; Siri, O.; Camplo, M.; Barthélémy, P.; Rocchi, P. Nucleoside-Lipid-Based Nanoparticles for Phenazine Delivery: A New Therapeutic Strategy to Disrupt Hsp27-eIF4E Interaction in Castration Resistant Prostate Cancer. Pharmaceutics 2021, 13, 623. https://doi.org/10.3390/pharmaceutics13050623

AMA Style

Ziouziou H, Paris C, Benizri S, Le TK, Andrieu C, Nguyen DT, Appavoo A, Taïeb D, Brunel F, Oueslati R, Siri O, Camplo M, Barthélémy P, Rocchi P. Nucleoside-Lipid-Based Nanoparticles for Phenazine Delivery: A New Therapeutic Strategy to Disrupt Hsp27-eIF4E Interaction in Castration Resistant Prostate Cancer. Pharmaceutics. 2021; 13(5):623. https://doi.org/10.3390/pharmaceutics13050623

Chicago/Turabian Style

Ziouziou, Hajer, Clément Paris, Sébastien Benizri, Thi K. Le, Claudia Andrieu, Dang T. Nguyen, Ananda Appavoo, David Taïeb, Frédéric Brunel, Ridha Oueslati, Olivier Siri, Michel Camplo, Philippe Barthélémy, and Palma Rocchi. 2021. "Nucleoside-Lipid-Based Nanoparticles for Phenazine Delivery: A New Therapeutic Strategy to Disrupt Hsp27-eIF4E Interaction in Castration Resistant Prostate Cancer" Pharmaceutics 13, no. 5: 623. https://doi.org/10.3390/pharmaceutics13050623

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