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Open AccessArticle

Improvement in the Anti-Tumor Efficacy of Doxorubicin Nanosponges in In Vitro and in Mice Bearing Breast Tumor Models

1
Dipartimento di Scienza e Tecnologia del Farmaco, University of Torino, 10125 Torino, Italy
2
Department of Health Sciences and Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), University of Eastern Piedmont (UPO), 28100 Novara, Italy
3
Department of Chemistry, University of Torino, 10125 Torino, Italy
4
Department of Clinical and Biological Sciences, University of Turin, 10125 Torino, Italy
*
Author to whom correspondence should be addressed.
Cancers 2020, 12(1), 162; https://doi.org/10.3390/cancers12010162
Received: 19 December 2019 / Revised: 7 January 2020 / Accepted: 8 January 2020 / Published: 9 January 2020
(This article belongs to the Special Issue Cancer Nanomedicine)
Doxorubicin (DOX) is an anthracycline widely used in cancer therapy and in particular in breast cancer treatment. The treatment with DOX appears successful, but it is limited by a severe cardiotoxicity. This work evaluated the in vitro and in vivo anticancer effect of a new formulation of β-cyclodextrin nanosponges containing DOX (BNS-DOX). The BNS-DOX effectiveness was evaluated in human and mouse breast cancer cell lines in vitro in terms of effect on cell growth, cell cycle distribution, and apoptosis induction; and in vivo in BALB-neuT mice developing spontaneous breast cancer in terms of biodistribution, cancer growth inhibition, and heart toxicity. BNS-DOX significantly inhibited cancer cell proliferation, through the induction of apoptosis, with higher efficiency than free DOX. The breast cancer growth in BALB-neuT mice was inhibited by 60% by a BNS-DOX dose five times lower than the DOX therapeutic dose, with substantial reduction of tumor neoangiogenesis and lymphangiogenesis. Biodistribution after BNS-DOX treatment revealed a high accumulation of DOX in the tumor site and a low accumulation in the hearts of mice. Results indicated that use of BNS may be an efficient strategy to deliver DOX in the treatment of breast cancer, since it improves the anti-cancer effectiveness and reduces cardiotoxicity. View Full-Text
Keywords: β-cyclodextrin nanosponges; doxorubicin; breast cancer; BALB-neuT mice; EPR effect β-cyclodextrin nanosponges; doxorubicin; breast cancer; BALB-neuT mice; EPR effect
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Argenziano, M.; Gigliotti, C.L.; Clemente, N.; Boggio, E.; Ferrara, B.; Trotta, F.; Pizzimenti, S.; Barrera, G.; Boldorini, R.; Bessone, F.; Dianzani, U.; Cavalli, R.; Dianzani, C. Improvement in the Anti-Tumor Efficacy of Doxorubicin Nanosponges in In Vitro and in Mice Bearing Breast Tumor Models. Cancers 2020, 12, 162.

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