Li Jian, Yoong Sia Lee, Goh Wei Jiang, Czarny Bertrand, Yang Zhi, Poddar Kingshuk, Dykas Michal M, Patra Abhijeet, Venkatesan T, Panczyk Tomasz, Lee Chengkuo, Pastorin Giorgia
Department of Pharmacy, National University of Singapore, Singapore.
NUS Graduate School for Integrative Sciences and Engineering, Centre for Life Sciences (CeLS), National University of Singapore, Singapore.
Int J Nanomedicine. 2015 Dec 15;10:7425-41. doi: 10.2147/IJN.S93810. eCollection 2015.
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.
碳纳米管（CNTs）的中空内部空间已被用于生物医学应用探索，比如作为防止药物失活的药物储存库。为了进一步将碳纳米管设计成用于控制释放货物分子的智能材料，我们提出了“金 - 碳纳米瓶”的概念。在将顺二氯二氨铂（II）（顺铂，CDDP）封装到碳纳米管中后，我们通过不同的可裂解连接键，即肼、酯和含二硫键的连接键，在碳纳米管的开口端共价连接金纳米颗粒（AuNPs）。与我们之前的研究相比，之前的研究中超过80%的顺铂在2小时内从碳纳米管中泄漏，而现在发现金纳米颗粒能显著将这种自发释放降低至<40%。此外，在模拟细胞内环境的还原条件下（即含有1 mM二硫苏糖醇 [DTT]），通过二硫键连接的金纳米颗粒封端的碳纳米管中顺铂的释放选择性地增加了两倍。我们用负载顺铂的金 - 碳纳米瓶处理人结肠腺癌细胞HCT116，并使用乳酸脱氢酶测定法检测细胞活力。有趣的是，我们发现与正常人胎儿肺成纤维细胞IMR - 90相比，带有可裂解二硫键的纳米瓶在HCT116中发挥了更强的细胞毒性作用。因此，我们推断我们内置二硫键的纳米瓶策略可以在高还原性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造成附带损害。
