Though progress in the use carbon nanotubes in medicine has been most encouraging for therapeutic and diagnostic applications, any translational success must involve overcoming the toxicological and surface functionalization challenges inherent in the use of such nanotubes. Ideally, a carbon nanotube-based drug delivery system would exhibit low toxicity, sustained drug release, and persist in circulation without aggregation. We report a carbon nanotube (CNT) coated with a biocompatible block-co-polymer composed of poly(lactide)-poly(ethylene glycol) (PLA-PEG) to reduce short-term and long-term toxicity, sustain drug release of paclitaxel (PTX), and prevent aggregation. The copolymer coating on the surface of CNTs significantly reduces in vitro toxicity in human umbilical vein endothelial cells (HUVEC) and U-87 glioblastoma cells. Moreover, coating reduces in vitro inflammatory response in rat lung epithelial cells. Compared to non-coated CNTs, in vivo studies show no long-term inflammatory response with CNT coated with PLA-PEG (CLP) and the surface coating significantly decreases acute toxicity by doubling the maximum tolerated dose in mice. Using polymer coatings, we can encapsulate PTX and release over one week to increase the therapeutic efficacy compared to free drugs. In vivo biodistribution and histology studies suggests a lower degree of aggregation in tissues in that CLP accumulate more in the brain and less in the spleen than the CNT-PLA (CL) formulation.

中文翻译：

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用于安全药物输送的多功能聚合物涂层碳纳米管

尽管碳纳米管在医学中的应用进展对于治疗和诊断应用来说是最令人鼓舞的，但任何转化成功都必须涉及克服使用此类纳米管所固有的毒理学和表面功能化挑战。理想情况下，基于碳纳米管的药物递送系统应表现出低毒性、持续的药物释放，并且持续循环而不聚集。我们报道了一种碳纳米管（CNT），涂有由聚丙交酯-聚乙二醇（PLA-PEG）组成的生物相容性嵌段共聚物，可降低短期和长期毒性，维持紫杉醇的药物释放(PTX)，并防止聚集。碳纳米管表面的共聚物涂层显着降低了人脐静脉内皮细胞（HUVEC）和U-87胶质母细胞瘤细胞的体外毒性。此外，涂层减少了大鼠肺上皮细胞的体外炎症反应。与未涂覆的碳纳米管相比，体内研究表明，涂有PLA-PEG（CLP）的碳纳米管没有长期炎症反应，并且表面涂层通过使小鼠最大耐受剂量加倍，显着降低了急性毒性。使用聚合物涂层，我们可以封装 PTX 并在一周内释放，从而与游离药物相比提高治疗效果。体内生物分布和组织学研究表明，与 CNT-PLA (CL) 制剂相比，CLP 在大脑中积累较多，在脾脏中积累较少，因此组织中的聚集程度较低。