p722 ferrocifen loaded lipid nanocapsules improve survival of murine xenografted-melanoma via a potentiation of apoptosis and an activation of CD8+ T lymphocytes

Solène Topin-Ruiz (1, 2) , Adélie Mellinger (1, 2) , Elise Lepeltier (1, 2) , Clara Bourreau (1, 2) , Juliette Fouillet (1, 2) , Jeremie Riou (1, 2) , Gérard Jaouen (3, 4, 5) , Ludovic Martin (1, 2) , Catherine Passirani (1, 2) , Nicolas Clere (1, 2)

1 MINT - Micro et Nanomédecines Translationnelles
2 IBS - Institut de Biologie en Santé (PHB-IRIS) [CHU Angers]
3 IPCM - Institut Parisien de Chimie Moléculaire
4 CHEMBIO - Chemical Biology
5 ENSCP - Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL

Metastatic melanoma is a malignant tumor with a poor prognosis. Recent new therapeutics improved the survival of patients at a metastatic stage. However, the low response rate to immunotherapy, explained in part by resistance to apoptosis, needs to develop new strategies. The ferrocifen family represents promising bioorganometallic molecules for melanoma treatment since they show potent anticancer properties. The aim of this study is (i) to evaluate the benefits of a strategy involving encapsulated p722 in lipid nanocapsules (LNC) in B16F10 melanoma mice models and (ii) to compare the beneficial effects with an existing therapy such as anti-CTLA4 mAb. Interestingly, LNC-p722 induces a significant decrease of melanoma cell viability. In vivo data shows a significant improvement in the survival rate and a slower tumor growth with p722-loaded LNC in comparison with anti-CTLA4 mAb. Western blots confirm that LNC-p722 potentiates intrinsic apoptotic pathway. Treatment with LNC-p722 significantly activates CD8+ T lymphocytes compared to treatment with anti-CTLA4 mAb. This study uncovers a new therapeutic strategy with encapsulated p722 to prevent B16F10 melanoma growth and to improve survival of treated mice.

Mots clés: Apoptosis; CD8 T lymphocytes; Ferrocifen; Metastatic melanoma

Domaines: Sciences pharmaceutiques

Solène Topin-Ruiz, Adélie Mellinger, Elise Lepeltier, Clara Bourreau, Juliette Fouillet, et al.. p722 ferrocifen loaded lipid nanocapsules improve survival of murine xenografted-melanoma via a potentiation of apoptosis and an activation of CD8+ T lymphocytes. International Journal of Pharmaceutics, 2021, 593, pp.120111. ⟨10.1016/j.ijpharm.2020.120111⟩. ⟨hal-03026310⟩