Department of Pharmacy, National University of Singapore, Science Drive 2, Singapore.
Department of Chemistry, National University of Singapore, Singapore.
Nanomedicine. 2014 Oct;10(7):1465-75. doi: 10.1016/j.nano.2014.01.004. Epub 2014 Jan 30.
Carbon nanotubes (CNTs) are promising drug delivery systems due to their external functionalizable surface and their hollowed cavity that can encapsulate several bioactive molecules. In this study, the chemotherapeutic drug cisplatin or an inert platinum(IV) complex were entrapped inside functionalized-multi-walled-CNTs and intravenously injected into mice to investigate the influence of CNTs on the biodistribution of Pt-based molecules. The platinum levels in vital organs suggested that functionalized-CNTs did not affect cisplatin distribution, while they significantly enhanced the accumulation of Pt(IV) sample in some tissues (e.g. in the lungs, suggesting their potential application in lung cancer therapy) and reduced both kidney and liver accumulation (thus decreasing eventual nephrotoxicity, a typical side effect of cisplatin). Concurrently, CNTs did not induce any intrinsic abnormal immune response or inflammation, as confirmed by normal cytokine levels and histological evaluations. Therefore, functionalized nanotubes represent an efficient nano-carrier to improve accumulation of Pt species in targeted tissues/organs. From the clinical editor: In this preclinical study functionalized carbon nanotubes are reported to be safe and efficient for targeted delivery of platinum-containing compounds in rodents. Approaches like this may improve the treatment of specific cancers, since platinum based chemotherapies are commonly used, yet limited by toxicity and relatively poor target tissue concentration.
碳纳米管(CNTs)由于其外部可功能化的表面和可以包裹几个生物活性分子的中空腔,是很有前途的药物输送系统。在这项研究中,化疗药物顺铂或惰性铂(IV)配合物被包裹在功能化多壁 CNT 内,并静脉注射到小鼠体内,以研究 CNT 对基于 Pt 的分子生物分布的影响。重要器官中的铂水平表明,功能化 CNT 不会影响顺铂的分布,而它们会显著增加某些组织中 Pt(IV)样品的积累(例如在肺部,这表明它们在肺癌治疗中的潜在应用),并减少肾脏和肝脏的积累(从而降低顺铂的潜在肾毒性,这是顺铂的典型副作用)。同时,CNTs 不会引起任何内在的异常免疫反应或炎症,这通过正常的细胞因子水平和组织学评估得到证实。因此,功能化纳米管代表了一种有效的纳米载体,可以提高靶向组织/器官中 Pt 物质的积累。临床编辑按:在这项临床前研究中,报告称功能化碳纳米管在啮齿动物中安全有效地靶向递送含铂化合物。这种方法可能会改善特定癌症的治疗效果,因为铂类化疗药物通常被使用,但由于毒性和相对较差的靶组织浓度而受到限制。