Enhanced efficacy of propranolol therapy for infantile hemangiomas based on a mesoporous silica nanoplatform through mediating autophagy dysfunction
Enhanced efficacy of propranolol therapy for infantile hemangiomas based on a mesoporous silica nanoplatform through mediating autophagy dysfunction
复制标题
基于介孔二氧化硅纳米平台通过介导自噬功能增强普萘洛尔治疗婴儿血管瘤的疗效
DOI：
10.1016/j.actbio.2020.02.033
复制
发表时间：
2020
影响因子：
9.7
通讯作者：
Zhang Dongsheng
中科院分区：
文献类型：
--
作者：
Wu Haiwei;Wang Xuan;Liang Hao;Zheng Jiawei;Huang Shengyun;Zhang Dongsheng
婴幼儿血管瘤是最常见的血管性肿瘤之一，若不及时治疗，可导致严重的并发症和死亡。普萘洛尔是目前治疗血管瘤的一线药物，但其潜在的副作用和给药频率高，迫切需要开发一种合适的普萘洛尔给药系统。在本研究中，我们制定了普萘洛尔传递系统的基础上介孔二氧化硅纳米粒子（PRN@MSN）和研究之间的相互作用的纳米粒子介导的自噬活性和改善PRN@MSN的治疗效果。结果表明，与游离普萘洛尔相比，PRN@MSN纳米粒在体内外均表现出更高的细胞毒性，可通过增加自噬体的形成和削弱自噬体的降解，诱导自噬体过度积聚。早期抑制自噬可减轻PRN@MSN的细胞毒性。ROS的产生对于纳米颗粒介导的自噬和细胞毒性是必不可少的，PRN@ MSN诱导的自噬功能障碍可以增强血管瘤干细胞的内质网（ER）应激。我们的研究揭示了一种基于介孔二氧化硅纳米平台的有前途的PRN递送系统，该系统可以诱导自噬功能障碍和过度的自噬体积累，以促进PRN治疗的疗效。PRN@MSN给药系统结合自噬调控可能成为血管瘤治疗的一种有前途的治疗模式。
Infantile hemangioma is one of the most common vascular tumors, which might result in morbidity and mortality without timely intervention. Propranolol is currently the first-line therapy for hemangiomas, but its potential side effects and high frequency of administration make it urgent to develop a suitable drug delivery system for propranolol. In the present study, we formulated a propranolol delivery system based on mesoporous silica nanoparticles (PRN@MSN) and investigated the interplay between autophagic activities mediated by nanoparticles and improved therapeutic efficacy of PRN@MSN. The results showed that PRN@MSN nanoparticles exhibited higher cytotoxicity compared with free propranolol in vitro and in vivo, which could induce excessive autophagosome accumulation through increased autophagosome formation and impaired autophagic degradation. Inhibition of autophagy in the early stage could attenuate the cytotoxicity of PRN@MSN. ROS generation was essential for nanoparticle-mediated autophagy and cytotoxicity, and PRN@MSN-induced autophagy dysfunction could enhance endoplasmic reticulum (ER) stress in hemangioma stem cells. Our study revealed a promising PRN delivery system based on a mesoporous silica nanoplatform that could induce autophagy dysfunction with excessive autophagosome accumulation to promote the therapeutic efficacy of PRN therapy. PRN@MSN drug delivery system combined with autophagy modulation may act as a promising treatment pattern in the treatment of hemangiomas.