School of Chemical Engineering, Sungkyunkwan University, Suwon, Gyeonggi 16419, Republic of Korea.
School of Chemical Engineering, Sungkyunkwan University, Suwon, Gyeonggi 16419, Republic of Korea.
Mater Sci Eng C Mater Biol Appl. 2019 Aug;101:464-471. doi: 10.1016/j.msec.2019.03.100. Epub 2019 Mar 27.
Curcumin shows a potential anticancer activity, as it is involved in signaling pathway suppressing β-catenin response transcription. In this study, the effects of curcumin released from the biocompatible and biodegradable polyaspartamide based micelles on colon cancer treatment via the Wnt/β-catenin signaling pathway are investigated. Hydrophobic octadecylamine (C) and hydrophilic O-(2-aminoethyl) polyethylene glycol (PEG) were grafted on a polysuccinimide (PSI) backbone for micelle formation. Folic acid (FA) was employed to facilitate the targeting activity to colon cancer cells and curcumin was conjugated via acid cleavable linkage, hydrazone (Hyd) to provide the pH sensitive drug release. Two types of micellar structures, Folate-PEG/Hyd-Curcumin/C-g-PSI (FA-Cur) and PEG/Hyd-Curcumin/C-g-PSI (NFA-Cur), were synthesized and their chemical structure was identified by H NMR spectroscopy. The cytotoxicity carried out by MTT assay informed that the cell viability of FA-Cur treated SW480 was much lower than that of NFA-Cur treated one at the concentration > 0.25 μg mL. Western blot assay showed that FA-Cur inhibited the target genes, cyclin D1 and c-myc, more strongly than NFA-Cur at the concentration > 0.5 μg mL. From these results, FA-Cur micelles are expected to be a promising candidate for colon anti-cancer via inhibiting Wnt/β-catenin pathway.
姜黄素显示出潜在的抗癌活性，因为它参与了抑制β-连环蛋白反应转录的信号通路。在这项研究中，研究了从生物相容性和可生物降解的聚天冬酰胺基胶束中释放的姜黄素通过 Wnt/β-连环蛋白信号通路对结肠癌治疗的影响。疏水性十八烷基胺 (C) 和亲水性 O-(2-氨基乙基)聚乙二醇 (PEG) 被接枝到聚琥珀酰亚胺 (PSI) 主链上以形成胶束。叶酸 (FA) 被用于促进对结肠癌细胞的靶向活性，并通过酸裂解键、腙 (Hyd) 将姜黄素共轭，以提供 pH 敏感的药物释放。合成了两种胶束结构，叶酸-PEG/Hyd-Curcumin/C-g-PSI (FA-Cur) 和 PEG/Hyd-Curcumin/C-g-PSI (NFA-Cur)，并通过 H NMR 光谱鉴定了它们的化学结构。MTT 测定的细胞毒性表明，FA-Cur 处理的 SW480 细胞的细胞活力远低于 NFA-Cur 处理的细胞，浓度>0.25μg/mL。Western blot 分析表明，FA-Cur 在浓度>0.5μg/mL 时比 NFA-Cur 更强烈地抑制了靶基因 cyclin D1 和 c-myc。从这些结果可以看出，FA-Cur 胶束有望通过抑制 Wnt/β-连环蛋白途径成为治疗结肠癌的有前途的候选药物。
