TAT peptide-modified cisplatin-loaded iron oxide nanoparticles for reversing cisplatin-resistant nasopharyngeal carcinoma
TAT peptide-modified cisplatin-loaded iron oxide nanoparticles for reversing cisplatin-resistant nasopharyngeal carcinoma
复制标题
TAT肽修饰的负载顺铂的氧化铁纳米颗粒用于逆转顺铂耐药的鼻咽癌
DOI：
10.1016/j.bbrc.2019.02.117
复制
发表时间：
2019
影响因子：
3.1
通讯作者：
Xie Minqiang
中科院分区：
文献类型：
--
作者：
Weng Huanhuan;Bejjanki Naveen Kumar;Zhang Juan;Miao Xiangwan;Zhong Ying;Li Hailiang;Xie Huifen;Wang Siqi;Li Quanming;Xie Minqiang
随着化疗持续延长鼻咽癌（NPC）患者的生命周期，顺铂（CDDP）的不良反应和耐药仍然是两大主要问题。本研究率先设计了超顺磁性氧化铁纳米颗粒（SPION）表面细胞穿透肽修饰的双机制抗癌体系，以提高CDDP对鼻咽癌细胞，特别是对CDDP耐药的鼻咽癌细胞的递送效果。CDDP和氧化铁纳米颗粒联合递送对逆转Fenton反应引起的CDDP耐药有意想不到的效果，与单独递送CDDP相比，HNE-1/DDP和CNE-2/DDP耐药细胞的半数最大抑制浓度（IC 50）分别平均降低85%和94%。在此基础上，TAT肽修饰（YGRKKRRQRRR）显著提高肿瘤细胞内摄取，通过减少CDDP治疗剂量，达到更好的疗效和最小化副作用的目的。此外，我们用荧光特异性标记CDDP，通过药物示踪检测细胞内纳米颗粒的摄取和机制研究。这种新型化合物为减少化疗副作用和逆转耐药鼻咽癌提供了一种有希望的治疗方法。
As chemo-radiotherapy continues to increase the lifespan of patients with nasopharyngeal carcinoma (NPC), adverse reaction and drug resistance remain two major problems when using cisplatin (CDDP). In this study, we took the lead in designing a dual-mechanism anti-cancer system modified with cell-penetrating peptide on the surface of superparamagnetic iron oxide nanoparticles (SPION) to enhance CDDP delivery efficacy to NPC cells, especially CDDP resistant NPC cells. The combinatorial delivery of CDDP and iron oxide nanoparticles showed an unexpected effect on reversal of CDDP resistance due to the Fenton reaction with an average decrease in the half maximal inhibitory concentration (IC 50) of 85% and 94% in HNE-1/DDP and CNE-2/DDP resistant cells respectively compared to CDDP alone. On this basis, modification with TAT peptide (YGRKKRRQRRR) significantly improved tumor intracellular uptake, devoting to better curative effects and minimized side effects by reducing CDDP therapeutic doses. Furthermore, we specifically labelled CDDP with fluorescence for detection of intracellular nanoparticles uptake and mechanism research through drug tracing. This novel compound provides a promising therapy for reducing chemotherapy side effects and reversing CDDP-resistant nasopharyngeal carcinoma.