摘要
摘 要:为解决白藜芦醇(Res)因水溶性小、稳定性差、生物利用度低而在临床的应用受到限制的问题,将叶酸-聚乙二醇-脂质体(FA-PEG-Lip)、介孔碳纳米管(MCN)和Res混合并超声处理,制备得到装载Res的FA-PEG-Lip包裹的MCN(FA-PEG-Lip@MCN/Res)纳米体系。所获得的FA-PEG-Lip@MCN/Res具有纳米级尺寸[宽:(80±10)nm;长:(600±100)nm]、负的表面电荷(-10.2 mV)、出色的载药量(131.59 mg/g MCN)、良好的溶液分散性和近红外(NIR)激光刺激-响应释放能力等特点。由于叶酸受体介导的靶向运输,FA-PEG-Lip@MCN/Res纳米体系可以高特异性地将所运载的Res转运到人乳腺癌细胞(MCF-7)。细胞增殖毒性试验表明,未装载药物的FA-PEG-Lip@MCN其本身生物相容性良好,适于作为药物载体。一系列细胞水平及活体水平的肿瘤治疗试验证明,在NIR激光照射下,该FA-PEG-Lip@MCN/Res纳米体系表现出良好的化疗/光热协同治疗作用,能够对肿瘤进行高效地杀伤。总而言之,该FA-PEG-Lip@MCN/Res纳米体系能够同时实现提高Res的水溶性、增强Res的稳定性、延长Res在小鼠体内的半衰期、叶酸受体靶向、NIR激光刺激-响应释放以及肿瘤协同治疗等诸多功能,有望进一步推动Res在临床的应用。
关键词:白藜芦醇;介孔碳纳米管;纳米脂质体;化疗/光热协同治疗;叶酸靶向
中图分类号:O657 文献标志码:A DOI: 10.3969/j.issn.1007-7146.2020.06.011
Abstract
Abstract: Resveratrol (Res) is a promising molecule for fighting cancer. However, the potential of the drug is immensely hindered by several limiting factors, including poor water solubility, limited chemical stability, and low bioavailability. In order to solve the above problems, we report a facile synthesis of a Res-loaded folate-terminated PEG-liposome (FA-PEG-Lip) coated mesoporous carbon nanotube (MCN) nanosystem (FA-PEG-Lip@MCN/Res) by simply sonicating Res and MCN in FA-PEG-Lip suspensions. The as-obtained FA-PEG-Lip@MCN/Res exhibits a nanoscale size [width: (80±10) nm, length: (600±100) nm], a negative surface potential (-10.2 mV), an excellent drug loading (131.59 mg/g MCN), good monodispersity and near infrared (NIR) laser stimulation-response release. Owing to folate receptor-mediated targeted delivery, the FA-PEG-Lip@MCN/Res nanosystem can deliver loaded Res to human breast cancer MCF-7 cells with high specificity. The cell toxicity viability shows that unloaded FA-PEG-Lip@MCN has no cytotoxicity, confirming its suitability as a drug vehicle. In addition, a systematic in vitro and in vivo experiments demonstrated that, under NIR laser irradiation, the FA-PEG-Lip@MCN/Res nanosystem exhibits highly efficient chemotherapy/photothermal synergistic therapy. All in all, the FA-PEG-Lip@MCN/Res nanosystem can simultaneously improve Res water solubility, enhance Res stability, extend plasma half-life of Res in mice, folate receptor targeting, NIR laser stimulation-response release, and synergistic tumor therapy, which may greatly promote the application of Res in clinical practice.
Key words: resveratrol; mesoporous carbon nanotube; nanoliposomes; chemo/photothermal synergistic therapy; folate targeting
李 璟,伍 旭,彭 倩,王晨旭,杨 凡.
基于装载白藜芦醇的脂质体包裹介孔碳纳米管用于靶向及近红外激光触发的化疗/光热协同肿瘤治疗[J]. 激光生物学报. 2020, 29(6): 550-560
LI Jing, WU Xu, PENG Qian, WANG Chenxu, YANG Fan.
Liposome Coated Mesoporous Carbon Nanotube with Resveratrol Loading for Targeted and Near-infrared Laser-triggered Chemo/Photothermal Synergistic Cancer Therapy[J]. Acta Laser Biology Sinica. 2020, 29(6): 550-560
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