Leonov Alexei P, Zheng Jiwen, Clogston Jeffrey D, Stern Stephan T, Patri Anil K, Wei Alexander
Department of Chemistry, Purdue University, West Lafayette, IN 47907, USA.
ACS Nano. 2008 Dec 23;2(12):2481-8. doi: 10.1021/nn800466c.
We address an outstanding issue associated with the biocompatibility of gold nanorods (GNRs), a promising agent for biomedical imaging and theragnostics. GNRs are typically prepared in the presence of cetyltrimethylammonium bromide (CTAB), a cationic surfactant whose rigorous removal is necessary due to its cytotoxicity and membrane-compromising properties. CTAB-stabilized GNRs can be partially purified by treatment with polystyrenesulfonate (PSS), an anionic polyelectrolyte often used as a surrogate peptizing agent, followed by chloroform extraction and ultrafiltration with minimal loss of dispersion stability. However, in vitro cytotoxicity assays of PSS-coated GNRs revealed IC(50) values in the low to submicromolar range, with subsequent studies indicating the source of toxicity to be associated with a persistent PSS-CTAB complex. Further exchange of CTAB-laden PSS with fresh polyelectrolyte greatly improves biocompatibility, to the extent that 85 microg/mL of "CTAB-free" GNRs (the highest level evaluated) has comparable toxicity to a standard phosphate buffer solution. Ironically, PSS is not effective by itself at stabilizing GNRs in CTAB-depleted suspensions: while useful as a detergent for GNR detoxification, it should be replaced by more robust coatings for long-term stability under physiological conditions.
我们解决了一个与金纳米棒（GNRs）生物相容性相关的突出问题，金纳米棒是生物医学成像和治疗诊断领域一种很有前景的物质。金纳米棒通常在十六烷基三甲基溴化铵（CTAB）存在的情况下制备，CTAB是一种阳离子表面活性剂，由于其细胞毒性和破坏膜的特性，必须将其彻底去除。CTAB稳定的金纳米棒可以通过用聚苯乙烯磺酸盐（PSS）处理进行部分纯化，PSS是一种阴离子聚电解质，常被用作替代胶溶剂，然后进行氯仿萃取和超滤，同时分散稳定性损失最小。然而，对PSS包覆的金纳米棒进行的体外细胞毒性试验显示，其半数抑制浓度（IC50）值在低至亚微摩尔范围内，随后的研究表明毒性来源与持续存在的PSS - CTAB复合物有关。用新鲜聚电解质进一步交换负载CTAB的PSS可大大提高生物相容性，以至于85微克/毫升的“无CTAB”金纳米棒（评估的最高水平）与标准磷酸盐缓冲溶液具有相当的毒性。具有讽刺意味的是，PSS本身在CTAB耗尽的悬浮液中并不能有效地稳定金纳米棒：虽然它可用作金纳米棒解毒的去污剂，但在生理条件下为实现长期稳定性，应该用更稳定的涂层来取代它。
