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Targeted delivery of SNX-2112 by polysaccharide-modified graphene oxide nanocomposites for treatment of lung cancer
Carbohydrate Polymers ( IF 10.7 ) Pub Date : 2018-01-05 , DOI: 10.1016/j.carbpol.2018.01.014
Xuan Liu , Xiaozhen Cheng , Fengzhe Wang , Longbao Feng , Yu Wang , Yanfang Zheng , Rui Guo

Graphene oxide (GO) is a promising material for biomedical applications, particularly in drug delivery, due to its exceptional chemical and physical properties. In this work, an innovative GO-based carrier was developed by modifying GO with chitosan (CHI) to improve the biocompatibility, and followed by the conjugation of hyaluronic acid (HA), the target ligand for CD44, to realize the specific recognition of tumor cells and improve the efficiency of anti-tumor drug delivery. The resulting product GO-CHI-HA was loaded with an anti-cancer drug SNX-2112, which is the Hsp90 inhibitor. The total release amount and release rate of SNX-2112 were significantly higher in acidic condition than in physiological condition. GO-CHI-HA with a low concentration had little impact on the lysis of red blood cells (RBCs) and blood coagulation and showed low toxicity in A549 cells and NHBE cells. The GO-CHI-HA/SNX-2112 proved to be effective in inhibiting and killing A549 cells while having lower cytotoxicity against normal human bronchial epithelial cells (NHBE cells). Furthermore, in vivo toxicity of the materials towards vital organs in SD rats were also studied through histological examinations and blood property analyses, the results of which showed that although inflammatory response was developed in the short-term, GO-CHI-HA/SNX-2112 caused no severe long-term injury. Therefore, this drug delivery system showed great potential as an effective and safe drug delivery system with little adverse side effects for cancer therapy.



中文翻译:

多糖修饰的氧化石墨烯纳米复合材料靶向递送SNX-2112用于治疗肺癌

氧化石墨烯(GO)由于其卓越的化学和物理特性,是用于生物医学应用(尤其是药物输送)的一种有前途的材料。在这项工作中,开发了一种创新的基于GO的载体,方法是用壳聚糖(CHI)修饰GO以改善生物相容性,然后缀合CD44的目标配体透明质酸(HA)以实现对肿瘤的特异性识别细胞并提高抗肿瘤药物传递的效率。所得产物GO-CHI-HA装有抗癌药SNX-2112,它是Hsp90抑制剂。在酸性条件下,SNX-2112的总释放量和释放速率明显高于生理条件。低浓度的GO-CHI-HA对红细胞(RBC)的溶解和血液凝固的影响很小,并且对A549细胞和NHBE细胞的毒性较低。GO-CHI-HA / SNX-2112被证明可有效抑制和杀死A549细胞,同时对正常人支气管上皮细胞(NHBE细胞)具有较低的细胞毒性。此外,还通过组织学检查和血液特性分析研究了该材料对SD大鼠重要器官的体内毒性,其结果显示,尽管短期内会发生炎症反应,但GO-CHI-HA / SNX-2112引起了没有严重的长期伤害。因此,该药物输送系统作为一种有效且安全的药物输送系统显示出巨大的潜力,并且对癌症治疗几乎没有不良副作用。

更新日期:2018-01-06
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