Nucleoside-Lipid-Based Nanoparticles for Phenazine Delivery: A New Therapeutic Strategy to Disrupt Hsp27-eIF4E Interaction in Castration Resistant Prostate Cancer
Hajer Ziouziou,
Clément Paris,
Sébastien Benizri,
Thi Khanh Le,
Claudia Andrieu,
Dang Tan Nguyen,
Ananda Appavoo,
David Taïeb,
Frédéric Brunel,
Ridha Oueslati,
Olivier Siri,
Michel Camplo,
Philippe Barthélémy,
Palma Rocchi
Affiliations
Hajer Ziouziou
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
Clément Paris
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
Sébastien Benizri
ARNA Laboratory, INSERM U1212/CNRS, UMR 5320, University of Bordeaux, F-33076 Bordeaux, France
Thi Khanh Le
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
Claudia Andrieu
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
Dang Tan Nguyen
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
Ananda Appavoo
ARNA Laboratory, INSERM U1212/CNRS, UMR 5320, University of Bordeaux, F-33076 Bordeaux, France
David Taïeb
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
Frédéric Brunel
Centre Interdisciplinaire de Nanoscience de Marseille, Aix-Marseille University, CNRS, UMR 7325, 163, Avenue de Luminy, F-13288 Marseille, France
Ridha Oueslati
Unit of Immunology Microbiology Environmental and Carcinogenesis (IMEC), Science Faculty of Bizerte, University of Carthage, 7000 Bizerte, Tunisia
Olivier Siri
Centre Interdisciplinaire de Nanoscience de Marseille, Aix-Marseille University, CNRS, UMR 7325, 163, Avenue de Luminy, F-13288 Marseille, France
Michel Camplo
Centre Interdisciplinaire de Nanoscience de Marseille, Aix-Marseille University, CNRS, UMR 7325, 163, Avenue de Luminy, F-13288 Marseille, France
Philippe Barthélémy
ARNA Laboratory, INSERM U1212/CNRS, UMR 5320, University of Bordeaux, F-33076 Bordeaux, France
Palma Rocchi
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
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.
