Department of Chemistry, Kansas State University, Manhattan, KS 66506, USA.
Department of Clinical Sciences, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA.
Nanoscale. 2020 Feb 14;12(6):4137-4149. doi: 10.1039/d0nr00039f. Epub 2020 Feb 5.
Recent progress in bioimaging nanotechnology has a great impact on the diagnosis, treatment, and prevention of diseases by enabling early intervention. Among different types of bioimaging modalities, contrast-enhanced magnetic resonance imaging using paramagnetic gadolinium-based molecular contrast agents (GBCAs) are most commonly used in clinic. However, molecular GBCAs distribute rapidly between plasma and interstitial spaces with short half-lives limiting its clinical impacts. To improve the properties of GBCAs, herein an effort has been put forth by incorporating GBCA into nanoscale system mimicking the property of red blood cell (RBC) that could facilitate contrast enhancement and prolong intraluminal retention in the body. The proposed nanoconstruct is made up of polymeric-core labeled with lipid conjugated GBCA followed by the imprint of the RBC membrane concealment layer to enhance stability and biocompatibility. Meanwhile, the confinement strategy of GBCA was implemented to accelerate magnetic properties of nanoconstruct providing longitudinal-relaxivity (r) to 12.78 ± 0.29 (mM s). Such improvement in r was further confirmed by enhanced contrast in the vascular angiography of the murine model. Given higher colloidal stability and tunable magnetic properties, nanoconstruct proposed herein is a promising platform technology for the applications where enhanced plasma residence time and magnetic properties are necessary for diagnosis and therapy.
近年来，生物成像纳米技术的进步通过实现早期干预，对疾病的诊断、治疗和预防产生了重大影响。在不同类型的生物成像方式中，使用顺磁性钆基分子造影剂（GBCA）的对比增强磁共振成像在临床上应用最为广泛。然而，分子 GBCA 半衰期短，在血浆和细胞间隙之间迅速分布，限制了其临床应用。为了改善 GBCA 的性能，本研究努力将 GBCA 整合到纳米级系统中，模拟红细胞（RBC）的特性，从而促进对比增强并延长体内管腔滞留。所提出的纳米结构由带有脂质共轭 GBCA 标记的聚合物核组成，然后是 RBC 膜隐蔽层的印迹，以提高稳定性和生物相容性。同时，实施了 GBCA 的约束策略，以加速纳米结构的磁性能，提供纵向弛豫率（r）为 12.78 ± 0.29（mM s）。通过在小鼠模型的血管造影中增强对比度，进一步证实了 r 的这种提高。鉴于更高的胶体稳定性和可调磁性能，本文提出的纳米结构是一种有前途的平台技术，适用于需要增强血浆停留时间和磁性能以进行诊断和治疗的应用。
