Avancini Greta, Guerrini Andrea, Ferroni Claudia, Tedesco Daniele, Ballestri Marco, Columbaro Marta, Menilli Luca, Reddi Elena, Costa Roberto, Leanza Luigi, Varchi Greta, Moret Francesca
Department of Biology, University of Padova, Padova, Italy.
Institute for Organic Synthesis and Photoreactivity, Italian National Research Council, Bologna, Italy.
Mater Sci Eng C Mater Biol Appl. 2021 Mar;122:111899. doi: 10.1016/j.msec.2021.111899. Epub 2021 Jan 23.
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.
乳腺癌（BC）的高侵袭性、耐药性和复发率主要归因于传统疗法无法同等程度地根除大量分化细胞和癌症干细胞（CSCs）。为提高BC治疗的有效性，我们报道了在水中合成新型角蛋白基纳米制剂，其负载有CSC特异性药物沙林霉素（SAL）、光敏剂二氢卟吩e6（Ce6）和维生素E醋酸酯（SAL/Ce6@kVEs），该制剂结合了释放SAL的能力以及光照时产生单线态氧的能力。对BC细胞系和富集CSC的乳腺球进行单药或联合治疗的体外实验表明，SAL/Ce6@kVEs可协同杀伤细胞，限制其自我更新能力，并通过根除CSCs降低干性潜能。对斑马鱼胚胎进行的体内实验证实了SAL纳米制剂干扰BC中失调的Wnt/β-连环蛋白信号通路的能力，从而确定了一个可进一步转化为临床前模型的靶点。
