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.

Hajer Ziouziou (1) , Clément Paris (1) , Sébastien Benizri (2) , Thi Khanh Le (1) , Claudia Andrieu (1) , Dang Tan Nguyen (1) , Ananda Appavoo (3) , David Taïeb (1) , Frédéric Brunel (3) , Ridha Oueslati (4) , Olivier Siri (5) , Michel Camplo (5) , Philippe Barthélémy (3) , Palma Rocchi (1)

1 CRCM - Centre de Recherche en Cancérologie de Marseille
2 ARNA - Régulations Naturelles et Artificielles
3 ARNA - Acides Nucléiques : Régulations Naturelle et Artificielle
4 Faculté des Sciences de Bizerte [Université de Carthage]
5 CINaM - Centre Interdisciplinaire de Nanoscience de Marseille

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.

Mots clés: dialkoxyphenazine; nanoformulation; nucleolipid; prostate cancer

Domaines: Chimie thérapeutique; Cancer; Urologie et Néphrologie; Sciences pharmaceutiques

Hajer Ziouziou, Clément Paris, Sébastien Benizri, Thi Khanh Le, Claudia Andrieu, et al.. 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), pp.623. ⟨10.3390/pharmaceutics13050623⟩. ⟨hal-03599172⟩