The peptidyl-prolyl cis/trans isomerase Pin1 positively regulates numerous cancer-driving pathways, and it is overexpressed in several malignancies, including high-grade serous ovarian cancer (HGSOC). The findings that all-trans retinoic acid (ATRA) induces Pin1 degradation strongly support that ATRA treatment might be a promising approach for HGSOC targeted therapy. Nevertheless, repurposing ATRA into the clinics for the treatment of solid tumors remains an unmet need mainly due to the insurgence of resistance and its ineffective delivery. In the present study, niosomes have been employed for improving ATRA delivery in HGSOC cell lines. Characterization of niosomes including hydrodynamic diameter, ζ-potential, morphology, entrapment efficiency and stability over time and in culture media was performed. Furthermore, pH-sensitiveness and ATRA release profile were investigated to demonstrate the capability of these vesicles to release ATRA in a stimuli-responsive manner. Obtained results documented a nanometric and monodispersed samples with negative ζ-potential. ATRA was efficiently entrapped, and a substantial release was observed in the presence of acidic pH (pH 5.5). Finally, unloaded niosomes showed good biocompatibility while ATRA-loaded niosomes significantly increased ATRA Pin1 inhibitory activity, which was consistent with cell growth inhibition. Taken together, ATRA-loaded niosomes might represent an appealing therapeutic strategy for HGSOC therapy.

pH-sensitive niosomes for ATRA delivery. A promising approach to inhibit Pin1 in high-grade serous ovarian cancer / Giuli, MARIA VALERIA; Hanieh, PATRIZIA NADIA; Forte, Jacopo; Fabiano, MARIA GIOIA; Mancusi, Angelica; Natiello, Bianca; Rinaldi, Federica; Del Favero, Elena; Grazia Ammendolia, Maria; Marianecci, Carlotta; Checquolo, Saula; Carafa, Maria. - In: INTERNATIONAL JOURNAL OF PHARMACEUTICS. - ISSN 0378-5173. - 649:(2024). [10.1016/j.ijpharm.2023.123672]

pH-sensitive niosomes for ATRA delivery. A promising approach to inhibit Pin1 in high-grade serous ovarian cancer

Maria Valeria Giuli
Co-primo
;
Patrizia Nadia Hanieh
Co-primo
;
Jacopo Forte;Maria Gioia Fabiano;Angelica Mancusi;Bianca Natiello;Federica Rinaldi
;
Carlotta Marianecci;Saula Checquolo
Ultimo
;
Maria Carafa
2024

Abstract

The peptidyl-prolyl cis/trans isomerase Pin1 positively regulates numerous cancer-driving pathways, and it is overexpressed in several malignancies, including high-grade serous ovarian cancer (HGSOC). The findings that all-trans retinoic acid (ATRA) induces Pin1 degradation strongly support that ATRA treatment might be a promising approach for HGSOC targeted therapy. Nevertheless, repurposing ATRA into the clinics for the treatment of solid tumors remains an unmet need mainly due to the insurgence of resistance and its ineffective delivery. In the present study, niosomes have been employed for improving ATRA delivery in HGSOC cell lines. Characterization of niosomes including hydrodynamic diameter, ζ-potential, morphology, entrapment efficiency and stability over time and in culture media was performed. Furthermore, pH-sensitiveness and ATRA release profile were investigated to demonstrate the capability of these vesicles to release ATRA in a stimuli-responsive manner. Obtained results documented a nanometric and monodispersed samples with negative ζ-potential. ATRA was efficiently entrapped, and a substantial release was observed in the presence of acidic pH (pH 5.5). Finally, unloaded niosomes showed good biocompatibility while ATRA-loaded niosomes significantly increased ATRA Pin1 inhibitory activity, which was consistent with cell growth inhibition. Taken together, ATRA-loaded niosomes might represent an appealing therapeutic strategy for HGSOC therapy.
2024
pin1; ovarian cancer; ATRA; niosomes; pH-sensitivity; nanomedicine
01 Pubblicazione su rivista::01a Articolo in rivista
pH-sensitive niosomes for ATRA delivery. A promising approach to inhibit Pin1 in high-grade serous ovarian cancer / Giuli, MARIA VALERIA; Hanieh, PATRIZIA NADIA; Forte, Jacopo; Fabiano, MARIA GIOIA; Mancusi, Angelica; Natiello, Bianca; Rinaldi, Federica; Del Favero, Elena; Grazia Ammendolia, Maria; Marianecci, Carlotta; Checquolo, Saula; Carafa, Maria. - In: INTERNATIONAL JOURNAL OF PHARMACEUTICS. - ISSN 0378-5173. - 649:(2024). [10.1016/j.ijpharm.2023.123672]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1693986
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