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.

小儿血管瘤是最常见的血管肿瘤之一，如果不及时干预，可能会导致发病和死亡。普萘洛尔目前是血管瘤的一线治疗方法，但是其潜在的副作用和给药频率高，迫切需要开发一种适用于普萘洛尔的药物输送系统。在本研究中，我们基于中孔二氧化硅纳米粒子（PRN @ MSN）配制了普萘洛尔递送系统，并研究了纳米粒子介导的自噬活性与改善的PRN @ MSN疗效之间的相互作用。结果表明，与游离普萘洛尔相比，PRN @ MSN纳米粒在体外和体内均表现出更高的细胞毒性，可通过增加自噬体形成和自噬降解受损来诱导过量的自噬体积累。早期自噬的抑制可以减弱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至关重要，而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中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，并带有过多的自噬体，从而促进PRN治疗的疗效。PRN @ MSN药物递送系统与自噬调节相结合可能是血管瘤治疗中一种有希望的治疗方式。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应激。我们的研究揭示了一种基于中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，并带有过多的自噬体，从而促进PRN治疗的疗效。PRN @ MSN药物递送系统与自噬调节相结合可能是血管瘤治疗中一种有希望的治疗方式。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应激。我们的研究揭示了一种基于中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，并带有过多的自噬体，从而促进PRN治疗的疗效。PRN @ MSN药物递送系统与自噬调节相结合可能是血管瘤治疗中一种有希望的治疗方式。