Everolimus (Eve) is an FDA approved drug that inhibits mammalian target of rapamycin (mTOR). It is employed in breast cancer treatment even if its responsiveness is controversial. In an attempt to increase Eve effectiveness, we have developed a novel Eve nanoformulation exploiting H-ferritin nanocages (HEve) to improve its subcellular delivery. We took advantage of the natural tumor targeting of H-Ferritin, which is mediated by the transferrin receptor-1 (TfR1). Breast cancer cells overexpressing TfR-1 were successfully recognized by H-Ferritin, displaying quick nanocage internalization. HEve has been tested and compared to Eve for in vitro efficacy in sensitive and resistant breast cancer cells. Nanoformulated Eve induced remarkable antiproliferative activity in vitro, making even resistant cell lines sensitive to Eve. Moreover, the antiproliferative activity of HEve is fully in accordance with cytotoxicity observed by cell death assay. Furthermore, the significant increase in anticancer efficacy displayed in HEve-treated samples is due to the improved drug accumulation, as demonstrated by UHPLC-MS/MS quantifications. Our findings suggest that optimizing Eve subcellular delivery, thanks to nanoformulation, determines its improved antitumor activity in a panel of Eve-sensitive or resistant breast cancer cell lines.
Everolimus Nanoformulation in Biological Nanoparticles Increases Drug Responsiveness in Resistant and Low-Responsive Breast Cancer Cell Lines / A. Bonizzi, M. Truffi, M. Sevieri, R. Allevi, L. Sitia, R. Ottria, L. Sorrentino, C. Sottani, S. Negri, E. Grignani, S. Mazzucchelli, F. Corsi. - In: PHARMACEUTICS. - ISSN 1999-4923. - 11:8(2019 Aug 02), pp. 384.1-384.14.
|Titolo:||Everolimus Nanoformulation in Biological Nanoparticles Increases Drug Responsiveness in Resistant and Low-Responsive Breast Cancer Cell Lines|
|Parole Chiave:||Everolimus; H-ferritin; breast cancer; nanoparticles|
|Settore Scientifico Disciplinare:||Settore BIO/10 - Biochimica|
Settore BIO/11 - Biologia Molecolare
Settore BIO/12 - Biochimica Clinica e Biologia Molecolare Clinica
Settore BIO/13 - Biologia Applicata
|Progetto:||Nanocages di ferritina per il delivery di agenti antitumorali in carcinomi mammari primari ed in metastasi cerebrali|
|Data di pubblicazione:||2-ago-2019|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.3390/pharmaceutics11080384|
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