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首页> 美国卫生研究院文献>International Journal of Nanomedicine >In vitro controlled release of cisplatin from gold-carbon nanobottles via cleavable linkages
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In vitro controlled release of cisplatin from gold-carbon nanobottles via cleavable linkages

机译：通过可裂解键从金-碳纳米瓶中体外控制顺铂的释放

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Carbon nanotubes’ (CNTs) hollow interior space has been explored for biomedical applications, such as drug repository against undesirable inactivation. To further devise CNTs as smart material for controlled release of cargo molecules, we propose the concept of “gold-carbon nanobottles”. After encapsulating cis-diammineplatinum(II) dichloride (cisplatin, CDDP) in CNTs, we covalently attached gold nanoparticles (AuNPs) at the open-tips of CNTs via different cleavable linkages, namely hydrazine, ester, and disulfide-containing linkages. Compared with our previous study in which more than 80% of CDDP leaked from CNTs in 2 hours, AuNPs were found to significantly decrease such spontaneous release to <40%. In addition, CDDP release from AuNP-capped CNTs via disulfide linkage was selectively enhanced by twofolds in reducing conditions (namely with 1 mM dithiothreitol [DTT]), which mimic the intracellular environment. We treated human colon adenocarcinoma cells HCT116 with our CDDP-loaded gold-carbon nanobottles and examined the cell viability using lactate dehydrogenase assay. Interestingly, we found that our nanobottles with cleavable disulfide linkage exerted stronger cytotoxic effect in HCT116 compared with normal human fetal lung fibroblast cells IMR-90. Therefore, we infer that our nanobottles strategy with inbuilt disulfide linkage could attain selective release of payload in highly reductive tumor tissues while avoiding collateral damage to normal tissues.
机译：碳纳米管（CNTs）的中空内部空间已被探索用于生物医学应用，例如用于防止不希望的失活的药物储存库。为了进一步将碳纳米管设计为可控制货物分子释放的智能材料，我们提出了“金碳纳米瓶”的概念。在将CNTs包裹二氯化顺式二氨铂（II）（cisplatin，CDDP）之后，我们通过不同的可裂解键（肼，酯和含二硫键）将金纳米颗粒（AuNPs）共价附着在CNT的开口尖端。与我们之前的研究相比，在2小时内，有80％以上的CDDP从CNT中泄漏出来，与之相比，AuNPs显着降低了此类自发释放至<40％。此外，在还原条件下（即用1 mM二硫苏糖醇[DTT]）模拟细胞内环境，通过二硫键从AuNP封端的CNTs中释放CDDP选择性提高了两倍。我们用载有CDDP的金-碳纳米瓶对人结肠腺癌细胞HCT116进行了处理，并使用乳酸脱氢酶测定法检查了细胞活力。有趣的是，我们发现具有可裂解二硫键的纳米瓶在HCT116中比正常人胎儿肺成纤维细胞IMR-90具有更强的细胞毒性作用。因此，我们推断具有内置二硫键的纳米瓶策略可以在高度还原的肿瘤组织中实现有效载荷的选择性释放，同时避免对正常组织的附带损害。

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