Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign , 600 South Mathews Avenue, Urbana, Illinois 61801, United States.
ACS Nano. 2013 Nov 26;7(11):9599-610. doi: 10.1021/nn4026228. Epub 2013 Oct 11.
Common methods of loading magnetic resonance imaging (MRI) contrast agents into nanoparticles often suffer from challenges related to particle formation, complex chemical modification/purification steps, and reduced contrast efficiency. This study presents a simple, yet advanced process to address these issues by loading gadolinium, an MRI contrast agent, exclusively on a liposome surface using a polymeric fastener. The fastener, so named for its ability to physically link the two functional components together, consisted of chitosan substituted with diethylenetriaminepentaacetic acid (DTPA) to chelate gadolinium, as well as octadecyl chains to stabilize the modified chitosan on the liposome surface. The assembly strategy, mimicking the mechanisms by which viruses and proteins naturally anchor to a cell, provided greater T1 relaxivity than liposomes loaded with gadolinium in both the interior and outer leaflet. Gadolinium-coated liposomes were ultimately evaluated in vivo using murine ischemia models to highlight the diagnostic capability of the system. Taken together, this process decouples particle assembly and functionalization and, therefore, has considerable potential to enhance imaging quality while alleviating many of the difficulties associated with multifunctional particle fabrication.
常见的将磁共振成像(MRI)造影剂加载到纳米颗粒中的方法常常受到与颗粒形成、复杂的化学修饰/纯化步骤以及降低的对比度效率相关的挑战。本研究提出了一种简单而先进的方法,通过使用聚合物紧固件将 MRI 造影剂钆仅加载到脂质体表面上来解决这些问题。这种紧固件因其能够将两个功能组件物理连接在一起而得名,它由壳聚糖取代二乙烯三胺五乙酸(DTPA)以螯合钆,以及十八烷基链以稳定修饰后的壳聚糖在脂质体表面上。组装策略模拟了病毒和蛋白质自然附着在细胞上的机制,与内部和外部叶层中装载钆的脂质体相比,提供了更高的 T1 弛豫率。最终使用小鼠缺血模型在体内评估了载钆脂质体,以突出该系统的诊断能力。总的来说,该过程解耦了颗粒的组装和功能化,因此具有很大的潜力可以提高成像质量,同时减轻与多功能颗粒制造相关的许多困难。