H-Ferritin-nanocaged olaparib: a promising choice for both BRCA-mutated and sporadic triple negative breast cancer

Abstract Poly(ADP-ribose) polymerase (PARP) inhibitors represent a promising strategy toward the treatment of triple-negative breast cancer (TNBC), which is often associated to genomic instability and/or BRCA mutations. However, clinical outcome is controversial and no benefits have been demonstrate...

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Autores principales:	S. Mazzucchelli, M. Truffi, F. Baccarini, M. Beretta, L. Sorrentino, M. Bellini, M. A. Rizzuto, R. Ottria, A. Ravelli, P. Ciuffreda, D. Prosperi, F. Corsi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/461d775565f14fa88350002a8cc0ece9
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spelling	oai:doaj.org-article:461d775565f14fa88350002a8cc0ece92021-12-02T15:05:44ZH-Ferritin-nanocaged olaparib: a promising choice for both BRCA-mutated and sporadic triple negative breast cancer10.1038/s41598-017-07617-72045-2322https://doaj.org/article/461d775565f14fa88350002a8cc0ece92017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07617-7https://doaj.org/toc/2045-2322Abstract Poly(ADP-ribose) polymerase (PARP) inhibitors represent a promising strategy toward the treatment of triple-negative breast cancer (TNBC), which is often associated to genomic instability and/or BRCA mutations. However, clinical outcome is controversial and no benefits have been demonstrated in wild type BRCA cancers, possibly due to poor drug bioavailability and low nuclear delivery. In the attempt to overcome these limitations, we have developed H-Ferritin nanoformulated olaparib (HOla) and assessed its anticancer efficacy on both BRCA-mutated and non-mutated TNBC cells. We exploited the natural tumor targeting of H-Ferritin, which is mediated by the transferrin receptor-1 (TfR1), and its physiological tropism toward cell nucleus. TNBC cell lines over-expressing TfR-1 were successfully recognized by H-Ferritin, displaying a fast internalization into the cells. HOla induced remarkable cytotoxic effect in cancer cells, exhibiting 1000-fold higher anticancer activity compared to free olaparib (Ola). Accordingly, HOla treatment enhanced PARP-1 cleavage, DNA double strand breaks and Ola delivery into the nuclear compartment. Our findings suggest that H-Ferritin nanoformulation strongly enhances cytotoxic efficacy of Ola as a stand-alone therapy in both BRCA-mutated and wild type TNBC cells, by promoting targeted nuclear delivery.S. MazzucchelliM. TruffiF. BaccariniM. BerettaL. SorrentinoM. BelliniM. A. RizzutoR. OttriaA. RavelliP. CiuffredaD. ProsperiF. CorsiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q S. Mazzucchelli M. Truffi F. Baccarini M. Beretta L. Sorrentino M. Bellini M. A. Rizzuto R. Ottria A. Ravelli P. Ciuffreda D. Prosperi F. Corsi H-Ferritin-nanocaged olaparib: a promising choice for both BRCA-mutated and sporadic triple negative breast cancer
description	Abstract Poly(ADP-ribose) polymerase (PARP) inhibitors represent a promising strategy toward the treatment of triple-negative breast cancer (TNBC), which is often associated to genomic instability and/or BRCA mutations. However, clinical outcome is controversial and no benefits have been demonstrated in wild type BRCA cancers, possibly due to poor drug bioavailability and low nuclear delivery. In the attempt to overcome these limitations, we have developed H-Ferritin nanoformulated olaparib (HOla) and assessed its anticancer efficacy on both BRCA-mutated and non-mutated TNBC cells. We exploited the natural tumor targeting of H-Ferritin, which is mediated by the transferrin receptor-1 (TfR1), and its physiological tropism toward cell nucleus. TNBC cell lines over-expressing TfR-1 were successfully recognized by H-Ferritin, displaying a fast internalization into the cells. HOla induced remarkable cytotoxic effect in cancer cells, exhibiting 1000-fold higher anticancer activity compared to free olaparib (Ola). Accordingly, HOla treatment enhanced PARP-1 cleavage, DNA double strand breaks and Ola delivery into the nuclear compartment. Our findings suggest that H-Ferritin nanoformulation strongly enhances cytotoxic efficacy of Ola as a stand-alone therapy in both BRCA-mutated and wild type TNBC cells, by promoting targeted nuclear delivery.
format	article
author	S. Mazzucchelli M. Truffi F. Baccarini M. Beretta L. Sorrentino M. Bellini M. A. Rizzuto R. Ottria A. Ravelli P. Ciuffreda D. Prosperi F. Corsi
author_facet	S. Mazzucchelli M. Truffi F. Baccarini M. Beretta L. Sorrentino M. Bellini M. A. Rizzuto R. Ottria A. Ravelli P. Ciuffreda D. Prosperi F. Corsi
author_sort	S. Mazzucchelli
title	H-Ferritin-nanocaged olaparib: a promising choice for both BRCA-mutated and sporadic triple negative breast cancer
title_short	H-Ferritin-nanocaged olaparib: a promising choice for both BRCA-mutated and sporadic triple negative breast cancer
title_full	H-Ferritin-nanocaged olaparib: a promising choice for both BRCA-mutated and sporadic triple negative breast cancer
title_fullStr	H-Ferritin-nanocaged olaparib: a promising choice for both BRCA-mutated and sporadic triple negative breast cancer
title_full_unstemmed	H-Ferritin-nanocaged olaparib: a promising choice for both BRCA-mutated and sporadic triple negative breast cancer
title_sort	h-ferritin-nanocaged olaparib: a promising choice for both brca-mutated and sporadic triple negative breast cancer
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/461d775565f14fa88350002a8cc0ece9
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H-Ferritin-nanocaged olaparib: a promising choice for both BRCA-mutated and sporadic triple negative breast cancer

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