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Self-Assembled Nanomicelles as Curcumin Drug Delivery Vehicles: Impact on Solitary Fibrous Tumor Cell Protein Expression and Viability
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2018-09-04 00:00:00 , DOI: 10.1021/acs.molpharmaceut.8b00655
Gianpaolo Dagrada 1 , Katia Rupel 2, 3 , Serena Zacchigna 3 , Elena Tamborini 1 , Silvana Pilotti 1 , Adalberto Cavalleri 4 , Loryn E Fechner 5 , Erik Laurini 6 , David K Smith 5 , Silvia Brich 1 , Sabrina Pricl 6
Affiliation  

Solitary fibrous tumors (SFTs) are rare soft tissue sarcomas that rely on several epithelial–mesenchymal transition (EMT) protein regulators for invasion/metastatic progression. Curcumin (CUR) has several pharmacological activities, including anticancer activity and the ability to suppress the EMT process. However, poor absorption, rapid metabolism, and side effects at high doses limit the clinical applications of CUR. Here we present the results obtained by treating SFT cells with free CUR and three different CUR-loaded nanomicelles (NMs), each of which has its surface decorated with different ligands. All CUR-loaded NMs were more efficient in suppressing SFT cell viability and expression of EMT markers than CUR alone. Combined treatments with the pan-histone deacetylase dual inhibitor SAHA revealed a differential ability in inhibiting EMT markers expression and SFT cell invasiveness, depending on the NM-ligand type. Finally, combinations of photodynamic therapy and CUR-loaded NM administrations resulted in almost complete SFT cell viability abrogation 24 h after laser irradiation.

中文翻译:

自组装纳米胶束作为姜黄素药物递送载体:对孤立性纤维瘤细胞蛋白表达和活力的影响

孤立性纤维瘤 (SFTs) 是一种罕见的软组织肉瘤,它依赖于几种上皮间质转化 (EMT) 蛋白调节因子来进行侵袭/转移。姜黄素 (CUR) 具有多种药理活性,包括抗癌活性和抑制 EMT 过程的能力。然而,吸收差、代谢快和高剂量副作用限制了CUR的临床应用。在这里,我们展示了通过用游离 CUR 和三种不同的 CUR 负载纳米胶束 (NMs) 处理 SFT 细胞获得的结果,每种纳米胶束的表面都装饰有不同的配体。所有加载 CUR 的 NMs 在抑制 SFT 细胞活力和 EMT 标志物表达方面比单独使用 CUR 更有效。与泛组蛋白去乙酰化酶双重抑制剂 SAHA 的联合治疗揭示了抑制 EMT 标志物表达和 SFT 细胞侵袭性的不同能力,这取决于 NM 配体类型。最后,光动力疗法和负载 CUR 的 NM 给药的组合导致激光照射后 24 小时几乎完全消除 SFT 细胞活力。
更新日期:2018-09-04
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