热敏型可注射水凝胶,负载姜黄素脂质体以增强抗肿瘤效果。
Thermo-sensitive injectable hydrogel loading with elemene-loaded liposomes for enhanced anti-tumor effect.
发表日期:2023 Apr 27
作者:
Yijing Li, Yanhui Zhu, Jiaqi Chen, Huahua Wang, Weiwei Zhi, Ziang Wang, Yanbin Guan, Baiyan Wang, Yongyan Jia, Shengnan Huang, Xiali Zhu
来源:
Cellular & Molecular Immunology
摘要:
由于肿瘤微环境的异质性和复杂性,组合疗法,特别是化疗和光热疗法(PTT)的组合受到越来越多的关注。然而,化疗小分子药物和光热剂的联合使用是一个关键问题。在这里,我们制备了一种新型热敏水凝胶,其中载有香砂草醚(ELE)和基于纳米氧化石墨烯(NGO)的脂质体,以增强联合治疗效果。ELE被应用作为化疗的模型药物,因为它是一种天然的倍半萜类药物,具有广谱和高效的抗肿瘤活性。NGO被应用作为药物载体和光热剂,因为它具有二维结构和高光热转化效率。NGO进一步经过甘草酸(GA)改性,以改善其水分散性、生物相容性和靶向肿瘤的能力。ELE通过GA改性的NGO(GA/NGO)装载,制备被称为ELE-GA/NGO-Lip的脂质体,进一步与壳聚糖(CS)溶液和β-甘油磷酸钠(β-GP)溶液混合,制备出被称为ELE-GA/NGO-Lip-gel的热敏水凝胶。所得到的ELE-GA/NGO-Lip-gel具有37℃的胶化温度、温度和pH响应的胶溶性和高光热转化效应。更重要的是,ELE-GA/NGO-Lip-gel在808nm激光照射下对SMMC-7721细胞具有相对较高的抗肿瘤效能。本研究为热敏注射水凝胶在联合肿瘤治疗中的应用提供了潜力平台。
Due to the heterogeneity and the complexity of the tumor microenvironment, combination therapy, especially the combination of chemotherapy and photothermal therapy (PTT), had received increasing attention. However, the co-delivery of small molecule drugs for chemotherapy and photothermal agents was a key issue. Herein, we prepared a novel thermo-sensitive hydrogel loading with elemene (ELE)-loaded and nano graphene oxide (NGO)-based liposomes for enhanced combined therapy. ELE was applied as the model drug for chemotherapy because it was a natural sesquiterpene drug with broad-spectrum and efficient antitumor activity. NGO was applied as drug carrier and photothermal agent simultaneously due to its two-dimensional structure and high photo-thermal conversion efficacy. NGO was further modified with glycyrrhetinic acid (GA) to improve its water dispersion, biocompatibility and tumor-targeting ability. ELE was loaded by GA-modified NGO (GA/NGO) to prepare the liposomes designated as ELE-GA/NGO-Lip, which was further mixed with chitosan (CS) solution and β-glycerin sodium phosphate (β-GP) solution to prepare the thermo-sensitive hydrogel designated as ELE-GA/NGO-Lip-gel. The obtained ELE-GA/NGO-Lip-gel had the gelling temperature of 37°C, temperature and pH-response gel dissolution and high photo-thermal conversion effect. More importantly, ELE-GA/NGO-Lip-gel upon 808 nm laser irradiation had relative high anti-tumor efficiency against SMMC-7721 cells in vitro. This research might provide a potent platform for the application of thermos-sensitive injectable hydrogel in combined tumor therapy.