di Leo Nicoletta, Battaglini Matteo, Berger Liron, Giannaccini Martina, Dente Luciana, Hampel Silke, Vittorio Orazio, Cirillo Giuseppe, Raffa Vittoria
Department of Biology, Università di Pisa, Pisa 56127, Italy.
Istituto di Scienze della Vita, Scuola Superiore Sant'Anna, 56127, Italy.
Eur J Pharm Biopharm. 2017 May;114:1-10. doi: 10.1016/j.ejpb.2016.12.024. Epub 2017 Jan 11.
We validated the anticancer potential of a nanoformulation made by (+)-catechin, gelatin and carbon nanotubes in terms of inhibition of cancer cell proliferation, migration and associated neo-angiogenesis. Gelatin was selected to stabilize the catechin without compromising its anti-oxidant potential and the carbon nanotubes were used to increase its intracellular bioavailability. The anticancer potential of the resulting nanohybrid was validated on an aggressive melanoma cell line, in vitro and in zebrafish xenotransplants. The nanohybrid strongly enhances the cytotoxic effect of (+)-catechin. At a concentration of (+)-catechin 50μg/ml, the nanohybrid inhibited the ability of melanoma cells to proliferate (100% increase of cell doubling time and severe impairment in zebrafish xenotransplants), to migrate (totally inhibition in vitro and 50% reduction of cell motility in zebrafish xenotransplants) and to induce neo-angiogenesis (100% inhibition in zebrafish xenotransplants). Conversely, the free (+)-catechin and carrier (CNT:gel) had no statistically significant effects over the control, at any concentration tested. Our results suggest that the use of the nanohybrid, able to improve the therapeutic efficacy of the catechins, could represent a successful strategy for a future clinical translation.
我们通过抑制癌细胞增殖、迁移及相关新生血管生成,验证了由(+)-儿茶素、明胶和碳纳米管制成的纳米制剂的抗癌潜力。选择明胶来稳定儿茶素,同时不损害其抗氧化潜力,并使用碳纳米管来提高其细胞内生物利用度。在体外和斑马鱼异种移植实验中,在侵袭性黑色素瘤细胞系上验证了所得纳米杂化物的抗癌潜力。该纳米杂化物显著增强了(+)-儿茶素的细胞毒性作用。在(+)-儿茶素浓度为50μg/ml时,纳米杂化物抑制了黑色素瘤细胞的增殖能力(细胞倍增时间增加100%,斑马鱼异种移植中严重受损)、迁移能力(体外完全抑制,斑马鱼异种移植中细胞运动性降低50%)以及诱导新生血管生成的能力(斑马鱼异种移植中100%抑制)。相反,在任何测试浓度下,游离的(+)-儿茶素和载体(碳纳米管:明胶)与对照组相比均无统计学显著影响。我们的结果表明,使用能够提高儿茶素治疗效果的纳米杂化物,可能是未来临床转化的一种成功策略。