Cohen Dana, Mashiach Reut, Houben Lothar, Galisova Andrea, Addadi Yoseph, Kain David, Lubart Alisa, Blinder Pablo, Allouche-Arnon Hyla, Bar-Shir Amnon
Department of Organic Chemistry, Weizmann Institute of Science, Rehovot 7610001, Israel.
Department of Chemical Research Support, Weizmann Institute of Science, Rehovot 7610001, Israel.
ACS Nano. 2021 Apr 27;15(4):7563-7574. doi: 10.1021/acsnano.1c01040. Epub 2021 Apr 19.
Nature-inspired nanosized formulations based on an imageable, small-sized inorganic core scaffold, on which biomolecules are assembled to form nanobiomimetics, hold great promise for both early diagnostics and developed therapeutics. Nevertheless, the fabrication of nanobiomimetics that allow noninvasive background-free mapping of pathological events with improved sensitivity, enhanced specificity, and multiplexed capabilities remains a major challenge. Here, we introduce paramagnetic glyconanofluorides as small-sized (<10 nm) glycomimetics for immunotargeting and sensitive noninvasive F magnetic resonance imaging (MRI) mapping of inflammation. A very short relaxation time (70 ms) of the fluorides was achieved by doping the nanofluorides' solid crystal core with paramagnetic Sm, resulting in a significant 8-fold enhancement in their F MRI sensitivity, allowing faster acquisition and improved detectability levels. The fabricated nanosized glycomimetics exhibit significantly enhanced uptake within activated immune cells, providing background-free mapping of inflammatory activity, demonstrated in both locally induced inflammation and clinically related neuropathology animal models. Fabricating two types of nanofluorides, each with a distinct chemical shift, allowed us to exploit the color-like features of F MRI to map, in real time, immune specificity and preferred targetability of the paramagnetic glyconanofluorides, demonstrating the approach's potential extension to noninvasive multitarget imaging scenarios that are not yet applicable for nanobiomimetics based on other nanocrystal cores.
基于可成像的小型无机核心支架构建的受自然启发的纳米制剂,生物分子组装在该支架上形成纳米生物模拟物,在早期诊断和先进治疗方面都具有巨大潜力。然而,制造能够以更高的灵敏度、增强的特异性和多重能力对病理事件进行无创无背景映射的纳米生物模拟物仍然是一项重大挑战。在此,我们引入顺磁性糖纳米氟化物作为小型(<10 nm)糖模拟物,用于免疫靶向和炎症的灵敏无创F磁共振成像(MRI)映射。通过用顺磁性Sm掺杂纳米氟化物的固体晶体核心,实现了氟化物非常短的弛豫时间(70 ms),使其F MRI灵敏度显著提高了8倍,从而能够更快地采集并提高检测水平。所制备的纳米尺寸糖模拟物在活化免疫细胞内的摄取显著增强,可提供炎症活动的无背景映射,这在局部诱导炎症和临床相关神经病理学动物模型中均得到了证实。制备两种具有不同化学位移的纳米氟化物,使我们能够利用F MRI的类似颜色特征实时映射顺磁性糖纳米氟化物的免疫特异性和优先靶向性,证明了该方法在无创多靶点成像场景中的潜在扩展,而这对于基于其他纳米晶核心的纳米生物模拟物来说尚未适用。