文献名： Keratin nanoparticles and photodynamic therapy enhance the anticancer stem cells activity of salinomycin

作者 ： Greta Avancini ^a1 ， Andrea Guerrini ^b1 ， Claudia Ferroni ^b ， Daniele Tedesco ^b ， Marco Ballestri ^b ， Marta Columbaro ^c ， Luca Menilli ^a ， Elena Reddi ^a ， Roberto Costa ^a ， Luigi Leanza ^a ， Greta Varchi ^b ， Francesca Moret ^a

^a Department of Biology, University of Padova, Padova, Italy

^b Institute for Organic Synthesis and Photoreactivity, Italian National Research Council, Bologna, Italy

^c IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy

摘要： The high rates of aggressiveness, drug resistance and relapse of breast cancer (BC) are mainly attributed to the inability of conventional therapies to equally eradicate bulk differentiated cells and cancer stem cells (CSCs). To improve the effectiveness of BC treatments, we report the in-water synthesis of novel keratin-based nanoformulations, loaded with the CSC-specific drug salinomycin (SAL), the photosensitizer  chlorin e6 (Ce6) and vitamin E acetate (SAL/Ce6@kVEs), which combine the capability of releasing SAL with the production of singlet oxygen upon light irradiation. In vitro  experiments on BC cell lines and CSC-enriched mammospheres exposed to single or combined therapies showed that SAL/Ce6@kVEs determine synergistic cell killing, limit their self-renewal capacity and decrease the stemness potential by eradication of CSCs. In vivo  experiments on zebrafish embryos confirmed the capacity of SAL nanoformulations to interfere with the Wnt/β-catenin signaling pathway, which is dysregulated in BC, thus identifying a target for further translation into pre-clinical models.

关键词： Salinomycin ； Keratin nanoparticle ； Photodynamic therapy ； Chlorin e6 ； Cancer stem cells ； Zebrafish embryo