Enhanced efficacy of propranolol therapy for infantile hemangiomas based on a mesoporous silica nanoplatform through mediating autophagy dysfunction
| Autor: | Xuan Wang, Shengyun Huang, Hao Liang, Dongsheng Zhang, Haiwei Wu, Jia-Wei Zheng |
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| Rok vydání: | 2020 |
| Předmět: |
Male
Autophagosome 0206 medical engineering Biomedical Engineering Antineoplastic Agents 02 engineering and technology Propranolol Biochemistry Biomaterials Hemangioma In vivo Autophagy Human Umbilical Vein Endothelial Cells Animals Humans Medicine Cytotoxicity Molecular Biology Drug Carriers Mice Inbred BALB C business.industry General Medicine Endoplasmic Reticulum Stress Silicon Dioxide 021001 nanoscience & nanotechnology medicine.disease 020601 biomedical engineering Drug delivery Cancer research Unfolded protein response Nanoparticles sense organs Reactive Oxygen Species 0210 nano-technology business Porosity Biotechnology medicine.drug |
| Zdroj: | Acta Biomaterialia. 107:272-285 |
| ISSN: | 1742-7061 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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