TY - JOUR
T1 - Anticancer activity of paclitaxel-loaded keratin nanoparticles in two-dimensional and perfused three-dimensional breast cancer models
AU - Foglietta, Federica
AU - Spagnoli, Giulio C.
AU - Muraro, Manuele Giuseppe
AU - Ballestri, Marco
AU - Guerrini, Andrea
AU - Ferroni, Claudia
AU - Aluigi, Annalisa
AU - Sotgiu, Giovanna
AU - Varchi, Greta
N1 - Funding Information:
FF gratefully thanks Post-Doctoral Fellowship 2016 of Fondazione Umberto Veronesi and the European Molecular Biology Organization (EMBO) Short-Term Fellowship (ASTF 621-2015) for financial support of her research grants. This work was also supported by the Investigator Grant of the Italian Association for Cancer Research (AIRC) 16740 to GV. The authors acknowledge Dr Marta Columbaro for TEM analysis of nanoparticles.
Publisher Copyright:
© 2018 Foglietta et al.
Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.
PY - 2018
Y1 - 2018
N2 - Purpose: Taxanes are highly effective cytotoxic drugs for progressing breast cancer treatment. However, their poor solubility and high toxicity urge the development of innovative formulations of potential clinical relevance. Materials and methods: By using a simple and straightforward aggregation method, we have generated paclitaxel (PTX) loaded in keratin nanoparticles (KER-NPs-PTX). Their activities were tested against human breast cancer MCF-7 and MDA MB 231 cell lines in conventional two-dimensional (2D) cultures and in a dynamic three-dimensional (3D) model with perfused bioreactor (p3D). Moreover, KER-NPs-PTX activity was compared to free PTX and to PTX loaded in albumin nanoparticles (HSA-NPs-PTX). Cell viability, induction of apoptosis, and gene expression analysis were used as readouts. Results: In 2D cultures, KER-NPs-PTX was able to inhibit tumor cell viability and to induce apoptosis similarly to PTX and HSA-NPs-PTX. In the p3D model, a lower sensitivity of tumor cells to treatments was observed. Importantly, only KER-NPs-PTX was able to induce a statistically significant increase in apoptotic cell percentages following 24 h treatment for MCF-7 (16.7±4.0 early and 11.3±4.9 late apoptotic cells) and 48 h treatment for MDA MB 231 (21.3±11.2 early and 10.5±1.8 late apoptotic cells) cells. These effects were supported, at least for MCF-7 cells, by significant increases in the expression of proapoptotic BAX gene (5.8±0.5) 24 h after treatment and of cleaved caspase 3 (CC3) protein. Conclusion: KER-NPs-PTX, generated by a simple procedure, is characterized by high water solubility and enhanced PTX-loading ability, as compared to HSA-NPs-PTX. Most importantly, it appears to be able to exert effective anticancer activities on breast cancer cells cultured in 2D or in p3D models.
AB - Purpose: Taxanes are highly effective cytotoxic drugs for progressing breast cancer treatment. However, their poor solubility and high toxicity urge the development of innovative formulations of potential clinical relevance. Materials and methods: By using a simple and straightforward aggregation method, we have generated paclitaxel (PTX) loaded in keratin nanoparticles (KER-NPs-PTX). Their activities were tested against human breast cancer MCF-7 and MDA MB 231 cell lines in conventional two-dimensional (2D) cultures and in a dynamic three-dimensional (3D) model with perfused bioreactor (p3D). Moreover, KER-NPs-PTX activity was compared to free PTX and to PTX loaded in albumin nanoparticles (HSA-NPs-PTX). Cell viability, induction of apoptosis, and gene expression analysis were used as readouts. Results: In 2D cultures, KER-NPs-PTX was able to inhibit tumor cell viability and to induce apoptosis similarly to PTX and HSA-NPs-PTX. In the p3D model, a lower sensitivity of tumor cells to treatments was observed. Importantly, only KER-NPs-PTX was able to induce a statistically significant increase in apoptotic cell percentages following 24 h treatment for MCF-7 (16.7±4.0 early and 11.3±4.9 late apoptotic cells) and 48 h treatment for MDA MB 231 (21.3±11.2 early and 10.5±1.8 late apoptotic cells) cells. These effects were supported, at least for MCF-7 cells, by significant increases in the expression of proapoptotic BAX gene (5.8±0.5) 24 h after treatment and of cleaved caspase 3 (CC3) protein. Conclusion: KER-NPs-PTX, generated by a simple procedure, is characterized by high water solubility and enhanced PTX-loading ability, as compared to HSA-NPs-PTX. Most importantly, it appears to be able to exert effective anticancer activities on breast cancer cells cultured in 2D or in p3D models.
KW - Breast cancer
KW - Keratin
KW - Nanoparticles
KW - Paclitaxel
KW - Perfused three-dimensional models
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U2 - 10.2147/IJN.S159942
DO - 10.2147/IJN.S159942
M3 - Article
C2 - 30214193
AN - SCOPUS:85055185305
VL - 13
SP - 4847
EP - 4867
JO - International Journal of Nanomedicine
JF - International Journal of Nanomedicine
SN - 1176-9114
ER -