Targeted delivery of amphotericin B to cells by using functionalized carbon nanotubes.
Targeted delivery of amphotericin B to cells by using functionalized carbon nanotubes.
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DOI：
10.1002/anie.200501613
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发表时间：
2005-10
影响因子：
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通讯作者：
Wei Wu;Sébastien Wieckowski;G. Pastorin;Monica Benincasa;Cédric Klumpp;J. Briand;R. Gennaro;M. Prato
中科院分区：
文献类型：
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作者：
Wei Wu;Sébastien Wieckowski;G. Pastorin;Monica Benincasa;Cédric Klumpp;J. Briand;R. Gennaro;M. Prato
功能化碳纳米管（f-CNTs）作为一种新的治疗性分子递送载体正日益受到人们的关注。事实上，碳纳米管（CNTs）已经被证明可以很容易地穿过细胞膜，并将肽、蛋白质和核酸输送到细胞中。这些创新载体具有较低的毒性，这一事实提高了它们在生物医学应用方面的潜力。本研究的目的是首先探索碳纳米管双重功能化的新策略；其次，评估荧光素和两性霉素B （AmB）功能化的碳纳米管的毒性和吸收特性，AmB是一种有效的抗真菌药物，但对哺乳动物细胞具有很高的毒性；第三，评估碳纳米管- AmB偶联物的抗真菌活性。AmB与碳纳米管的偶联有几个优点：1)增加了分子的溶解度，减少了导致药物高毒性的聚集现象；ii)由于CNTs的细胞穿透能力提高了功效；iii)对不同类型细胞的抗真菌/毒性活性的调节。结果表明，用异硫氰酸荧光素和两性霉素B （AmB）功能化的多壁碳纳米管可以迅速被哺乳动物细胞内化，而不像用未偶联的AmB处理时那样具有毒性作用。此外，该修饰药物比天然AmB具有更高的抗真菌活性。
Functionalized carbon nanotubes (f-CNTs) are attracting increasing attention as new vectors for the delivery of therapeutic molecules. In fact, carbon nanotubes (CNTs) have been shown to cross cell membranes easily and to deliver peptides, proteins, and nucleic acids into cells. These innovative carriers present a lower toxicity, a fact that boosts their potential for biomedical applications. The aim of the work here described was first to explore a new strategy for the double functionalization of CNTs, secondly, to assess the toxicity and uptake characteristics of CNTs functionalized with fluorescein and amphotericin B (AmB), an effective antifungal drug, which is however highly toxic to mammalian cells, and thirdly, to evaluate the antifungal activity of CNT–AmB conjugates. Conjugation of AmB to CNTs could have several advantages: i) increased solubility of the molecule with decreased aggregation phenomena that cause the high toxicity of the drug; ii) improved efficacy owing to the cell-penetrating capacity of the CNTs; and iii) modulation of the antifungal/toxic activity against different types of cells. The results obtained indicate that multiwalled carbon nanotubes functionalized with fluorescein isothiocyanate and amphotericin B (AmB), are rapidly internalized by mammalian cells without the toxic effects typically displayed upon treatment with unconjugated AmB. Furthermore, the modified drug exhibits a higher antifungal activity than native AmB.