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Open AccessArticle

Everolimus Nanoformulation in Biological Nanoparticles Increases Drug Responsiveness in Resistant and Low-Responsive Breast Cancer Cell Lines

1
Nanomedicine Laboratory, Department of Biomedical and Clinical Sciences “Luigi Sacco”, Università di Milano, 20157 Milano, Italy
2
Environmental Research Center, ICS MAUGERI SPA SB, Institute of Pavia, IRCCS, 27100 Pavia, Italy
3
Breast Unit, Istituti Clinici Scientifici Maugeri IRCCS, 27100 Pavia, Italy
*
Authors to whom correspondence should be addressed.
Pharmaceutics 2019, 11(8), 384; https://doi.org/10.3390/pharmaceutics11080384
Received: 31 May 2019 / Revised: 17 July 2019 / Accepted: 29 July 2019 / Published: 2 August 2019
(This article belongs to the Special Issue Bioinspired Design in Drug Delivery)
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Abstract

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. View Full-Text
Keywords: breast cancer; Everolimus; nanoparticles; H-ferritin breast cancer; Everolimus; nanoparticles; H-ferritin
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Bonizzi, A.; Truffi, M.; Sevieri, M.; Allevi, R.; Sitia, L.; Ottria, R.; Sorrentino, L.; Sottani, C.; Negri, S.; Grignani, E.; Mazzucchelli, S.; Corsi, F. Everolimus Nanoformulation in Biological Nanoparticles Increases Drug Responsiveness in Resistant and Low-Responsive Breast Cancer Cell Lines. Pharmaceutics 2019, 11, 384.

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