Yang Xi, Li Zhaojun, Wu Qinjie, Chen Shouchun, Yi Cheng, Gong Changyang
a Department of Medical Oncology, Cancer Center, and State Key Laboratory of Biotherapy , West China Hospital, Sichuan University , Chengdu , China.
b Department of Radiotherapy , Hainan General Hospital , Haikou , China.
Drug Deliv. 2017 Nov;24(1):1526-1536. doi: 10.1080/10717544.2017.1384863.
Active targeting nanoparticles were developed to simultaneously codeliver tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and Curcumin (Cur). In the nanoparticles (TRAIL-Cur-NPs), TRAIL was used as both active targeting ligand and therapeutic agent, and Cur could upregulate death receptors (DR4 and DR5) to increase the apoptosis-inducing effects of TRAIL. Compared with corresponding free drugs, TRAIL-Cur-NPs group showed enhanced cellular uptake, cytotoxicity and apoptosis induction effect on HCT116 colon cancer cells. In addition, in vivo anticancer studies suggested that TRAIL-Cur-NPs had superior therapeutic effect on tumors without obvious toxicity, which was mainly due to the high tumor targeting and synergistic effect of TRAIL and Cur. The synergistic mechanism of improved antitumor efficacy was proved to be upregulation of DR4 and DR5 in tumor cells induced by Cur. Thus, the prepared codelivery nanoparticles may have potential applications in colorectal cancer therapy.
活性靶向纳米颗粒被研发用于同时共递送肿瘤坏死因子相关凋亡诱导配体（TRAIL）和姜黄素（Cur）。在纳米颗粒（TRAIL-Cur-NPs）中，TRAIL既作为活性靶向配体又作为治疗剂，而Cur可以上调死亡受体（DR4和DR5）以增强TRAIL的凋亡诱导作用。与相应的游离药物相比，TRAIL-Cur-NPs组对HCT116结肠癌细胞显示出增强的细胞摄取、细胞毒性和凋亡诱导作用。此外，体内抗癌研究表明，TRAIL-Cur-NPs对肿瘤具有优异的治疗效果且无明显毒性，这主要归因于TRAIL和Cur的高肿瘤靶向性和协同作用。改善抗肿瘤疗效的协同机制被证明是由Cur诱导肿瘤细胞中DR4和DR5的上调。因此，所制备的共递送纳米颗粒可能在结直肠癌治疗中具有潜在应用。
