Department of Oncology, The First Affiliated Hospital of Zhengzhou University , 1 Jianshe Eastern Road, Zhengzhou 450052, Henan, China.
Department of Chemical and Biomolecular Engineering and Institute for NanoBioTechnology, Johns Hopkins University , Baltimore, Maryland 21218, United States.
ACS Nano. 2017 Jan 24;11(1):797-805. doi: 10.1021/acsnano.6b07196. Epub 2017 Jan 11.
Gadolinium (Gd)-based compounds and materials are the most commonly used magnetic resonance imaging (MRI) contrast agents in the clinic; however, safety concerns associated with their toxicities in the free ionic form have promoted the development of new generations of metal-free contrast agents. Here we report a supramolecular strategy to convert an FDA-approved anticancer drug, Pemetrexed (Pem), to a molecular hydrogelator with inherent chemical exchange saturation transfer (CEST) MRI signals. The rationally designed drug-peptide conjugate can spontaneously associate into filamentous assemblies under physiological conditions and consequently form theranostic supramolecular hydrogels for injectable delivery. We demonstrated that the local delivery and distribution of Pem-peptide nanofiber hydrogels can be directly assessed using CEST MRI in a mouse glioma model. Our work lays out the foundation for the development of drug-constructed theranostic supramolecular materials with an inherent CEST MRI signal that enables noninvasive monitoring of their in vivo distribution and drug release.
镝（Gd）基化合物和材料是临床上最常用的磁共振成像（MRI）对比剂；然而，其游离离子形式的毒性相关的安全问题促使了新一代无金属对比剂的发展。在这里，我们报告了一种超分子策略，将一种已获得 FDA 批准的抗癌药物培美曲塞（Pem）转化为具有固有化学交换饱和转移（CEST）MRI 信号的分子凝胶剂。合理设计的药物-肽缀合物可以在生理条件下自发缔合形成纤维状组装体，从而形成用于可注射递送的治疗性超分子水凝胶。我们证明，在小鼠脑胶质瘤模型中，可以使用 CEST MRI 直接评估 Pem-肽纳米纤维水凝胶的局部递送和分布。我们的工作为开发具有固有 CEST MRI 信号的药物构建治疗性超分子材料奠定了基础，该信号可实现对其体内分布和药物释放的非侵入性监测。
