Gao Xiang, Wang Bilan, Wu Qinjie, Wei Xiawei, Zheng Fengjin, Men Ke, Shi Huashan, Huang Ning, Wei Yuquan, Gong Changyang
J Biomed Nanotechnol. 2015 Apr;11(4):578-89. doi: 10.1166/jbn.2015.1964.
Paclitaxel (PTX) is efficacious in treating various solid tumors. However, the severe adverse effects of its present formulation (Cremophor EL and ethanol) and the development of drug resistance by the activation of nuclear factor-κB (NF-κB) reduce the anti-tumor activities of PTX. Curcumin (Cur) demonstrates anti-tumor activity by means of antiangiogenesis and induction of apoptosis as well as suppression of the activity of NF-κB. Therefore, to improve its antitumor activity and eliminate the toxicity of the commercial formulation of PTX, we prepared biodegradable monomethoxy poly(ethyleneglycol)-poly(ε-caprolactone) (MPEG-PCL) micelles to co-deliver PTX and Cur using a solid dispersion method. The mixed PTX and Cur polymeric micelles (PTX-Cur-M) produced were monomorphous micelles of 38 nm in diameter that released PTX and Cur for an extended period of time and induced cell apoptosis in vitro. In addition, the PTX-Cur-M exhibited anti-angiogenic activity in vitro and in vivo. Furthermore, the therapeutic efficacy of PTX-Cur-M in a mouse model of colon cancer was evaluated. PTX-Cur-M micelles produced significantly more inhibition of tumor growth than Cur micelles (Cur-M) and PTX micelles (PTX-M) alone at the same dose (P < 0.05 and P < 0.05, respectively). Immunohistochemical and immunofluorescent analyses demonstrated that PTX-Cur-M enhanced tumor cell apoptosis and inhibited angiogenesis to a greater extent than control treatment. Our data suggested that PTX-Cur-M may have potential clinical applications in cancer therapy.
紫杉醇（PTX）对多种实体瘤有效。然而，其现有制剂（聚氧乙烯蓖麻油和乙醇）的严重不良反应以及通过激活核因子-κB（NF-κB）产生的耐药性降低了PTX的抗肿瘤活性。姜黄素（Cur）通过抗血管生成、诱导细胞凋亡以及抑制NF-κB的活性来展现抗肿瘤活性。因此，为了提高其抗肿瘤活性并消除PTX商业制剂的毒性，我们采用固体分散法制备了可生物降解的单甲氧基聚（乙二醇）-聚（ε-己内酯）（MPEG-PCL）胶束，以共同递送PTX和Cur。所制备的PTX与Cur混合聚合物胶束（PTX-Cur-M）为直径38 nm的单分散胶束，能长时间释放PTX和Cur，并在体外诱导细胞凋亡。此外，PTX-Cur-M在体外和体内均表现出抗血管生成活性。此外，还评估了PTX-Cur-M在结肠癌小鼠模型中的治疗效果。在相同剂量下，PTX-Cur-M胶束对肿瘤生长的抑制作用明显大于单独的Cur胶束（Cur-M）和PTX胶束（PTX-M）（分别为P < 0.05和P < 0.05）。免疫组织化学和免疫荧光分析表明，与对照治疗相比，PTX-Cur-M能更大程度地增强肿瘤细胞凋亡并抑制血管生成。我们的数据表明，PTX-Cur-M在癌症治疗中可能具有潜在的临床应用价值。
