GSH triggered intracellular aggregated-cisplatin-loaded iron oxide nanoparticles for overcoming cisplatin resistance in nasopharyngeal carcinoma
GSH triggered intracellular aggregated-cisplatin-loaded iron oxide nanoparticles for overcoming cisplatin resistance in nasopharyngeal carcinoma
复制标题
GSH触发细胞内聚集的负载顺铂的氧化铁纳米颗粒克服鼻咽癌的顺铂耐药性
DOI：
10.1177/0885328220982151
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发表时间：
2021-01-05
影响因子：
2.9
通讯作者：
Xie, Minqiang
中科院分区：
文献类型：
--
作者：
Bejjanki, Naveen Kumar;Xu, Hongfa;Xie, Minqiang
含铂联合放化疗是治疗鼻咽癌最常用的方法。然而，脱靶效应和低效率是关于这种方法的两个主要问题。因此，迫切需要探索新的治疗模式，以满足临床标准。本研究以磁性氧化铁纳米粒子（Fe 3 O 4）为载体，经表面修饰叶酸（FA）和胞内聚集肽（Cys（StBu）-Lys-CBT）修饰，构建了一种新型的顺铂（CDDP）磁性氧化铁纳米粒子（FA-MNP-CDDP-CBT）抗癌给药系统。FA-MNP-CDDP-CBT对HNE-1细胞和HNE-1/DDP耐药细胞的半数抑制浓度（IC 50）分别比CDDP单药降低40.9%和59.1%。此外，FA-MNP-CDDP-CBT还显示出上级靶向摄取效果和较高的ROS产生。Western blot和流式细胞仪检测结果显示，转染后的鼻咽癌细胞凋亡率明显增加。因此，这种新设计的纳米系统提供了一种简便的方法，以提高抗肿瘤活性，减少化疗的副作用，最大限度地减少全身毒性，并逆转CDDP治疗耐药，这可能是提出了在未来的原发性或继发性化疗耐药的NPC患者。
Platinum-based combined chemo-radiotherapy is the most commonly used approach against Nasopharyngeal carcinoma (NPC). However, off target effect and poor efficiency are the two main concerns regarding this approach. Therefore, it is an urgent need to explore novel therapeutic modalities to meet clinically standards. In this work we have established a new anti-cancer drug delivery system, composed of cisplatin (CDDP)-loaded magnetic iron oxide nanoparticles (Fe3O4), further functionalized with surface modification of folic acid (FA) and intracellular aggregation ability peptide (Cys(StBu)-Lys-CBT), named as (FA-MNP-CDDP-CBT). FA-MNP-CDDP-CBT was much more effective on the reversal of CDDP resistance with an average reduction in half maximal inhibitory concentration (IC 50) of 40.9% and 59.1% in HNE-1 cells and HNE-1/DDP resistant cells respectively compared to CDDP alone. Moreover, FA-MNP-CDDP-CBT had also shown a superior targeted uptake effect and higher ROS generation. Convincingly, we observed a remarkable increase in the apoptosis rate of NPC cells by using western blot and flow cytometry. Thus, this newly design nano-system provides a facile approach to enhance the antitumor activity by reducing the side effects of chemotherapy, minimizing systemic toxicity, and reversing CDDP treatment resistance, which could be proposed for NPC patients with primary or secondary chemo-resistance in the future.