Center for Molecular Imaging Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
Molecular Imaging Program at Stanford (MIPS), Bio-X Program, and Department of Radiology, Canary Center at Stanford for Cancer Early Detection, Stanford University, Stanford, CA, 94305-5344, USA.
Adv Mater. 2021 Apr;33(16):e2006902. doi: 10.1002/adma.202006902. Epub 2021 Mar 12.
Development of novel nanomaterials for disease theranostics represents an important direction in chemistry and precision medicine. Fluorescent molecular probes in the second near-infrared window (NIR-II, 1000-1700 nm) show high promise because of their exceptional high detection sensitivity, resolution, and deep imaging depth. Here, a sharp pH-sensitive self-assembling cyclopeptide-dye, SIMM1000, as a smart nanoprobe for NIR-II imaging of diseases in living animals, is reported. This small molecule assembled nanoprobe exhibits smart properties by responding to a sharp decrease of pH in the tumor microenvironment (pH 7.0 to 6.8), aggregating from small nanoprobe (80 nm at pH 7.0) into large nanoparticles (>500 nm at pH 6.8) with ≈20-30 times enhanced fluorescence compared with the non-self-assembled CH-4T. It yields micrometer-scale resolution in blood vessel imaging and high contrast and resolution in bone and tumor imaging in mice. Because of its self-aggregation in acidic tumor microenvironments in situ, SIMM1000 exhibits high tumor accumulation and extremely long tumor retention (>19 days), while being excretable from normal tissues and safe. This smart self-assembling small molecule strategy can shift the paradigm of designing new nanomaterials for molecular imaging and drug development.
新型纳米材料的开发用于疾病治疗和诊断代表了化学和精准医学的一个重要方向。近红外二区（NIR-II，1000-1700nm）的荧光分子探针因其出色的高检测灵敏度、分辨率和深成像深度而具有很高的应用前景。在这里，我们报道了一种尖锐 pH 敏感的自组装环肽-染料 SIMM1000，它是一种用于活体动物疾病的近红外二区成像的智能纳米探针。这种小分子组装的纳米探针通过响应肿瘤微环境中 pH 值的急剧下降（pH 7.0 至 6.8）表现出智能特性，从小探针（pH 7.0 时为 80nm）聚集为大纳米颗粒（pH 6.8 时为>500nm），与非自组装的 CH-4T 相比，荧光强度增强约 20-30 倍。它可以在血管成像中实现微米级分辨率，并在小鼠的骨骼和肿瘤成像中提供高对比度和高分辨率。由于其在酸性肿瘤微环境中的原位自聚集，SIMM1000 表现出高肿瘤积累和极长的肿瘤保留时间（>19 天），同时可以从正常组织中排出且安全。这种智能自组装小分子策略可以改变设计用于分子成像和药物开发的新型纳米材料的范式。
