State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun 130012, P.R. China.
China-Japan Union Hospital of Jilin University, Key Laboratory of Lymphatic Surgery Jilin Province, Jilin Engineering Laboratory for Lymphatic Surgery Jilin Province, Changchun 130031, P. R. China.
Nano Lett. 2022 Oct 12;22(19):7965-7975. doi: 10.1021/acs.nanolett.2c03311. Epub 2022 Sep 27.
The renal-clearable aspect of imaging agent with minimum toxicity issues and side effects is essential for clinical translation, yet clinical near-infrared-I/II (NIR-I/II) fluorophores with timely renal-clearance pathways are very limited. Herein, we rationally develop the cyanine-protein composite strategy through covalent bonding of β-lactoglobulin (β-LG) and chloride-cyanine dye to produce a brilliant and stable NIR-I/II fluorophore (e.g., β-LG@IR-780). The β-LG acts as a protecting shell with small molecular weight (18.4 kDa) and ultrasmall size (<5 nm), thus endowing the β-LG@IR-780 with excellent biocompatibility and renal excretion. Our β-LG@IR-780 probe enables noninvasive and precise NIR-II visualization of the physiological and pathological conditions of the vascular and lymphatic drainage system, facilitating intraoperative imaging-guided surgery and postoperative noninvasive monitoring. The minimum accumulation of our probes in the main organs improves the overall biosafety. This study provides a facile methodology for new-generation NIR-II fluorophores and largely improves the brightness and pharmacokinetics of small molecular dyes.
对于临床转化而言，具有最小毒性问题和副作用的可肾脏清除的造影剂具有重要意义，但具有及时肾脏清除途径的临床近红外 I/II（NIR-I/II）荧光团非常有限。在此，我们通过β-乳球蛋白（β-LG）和氯花青染料的共价键合，合理地开发了菁染料-蛋白复合物策略，从而产生了明亮且稳定的近红外 I/II 荧光团（例如，β-LG@IR-780）。β-LG 作为具有小分子量（18.4 kDa）和超小尺寸（<5 nm）的保护壳，使β-LG@IR-780具有出色的生物相容性和肾脏排泄能力。我们的β-LG@IR-780 探针能够非侵入性且精确地可视化血管和淋巴引流系统的生理和病理状况，有助于术中成像引导手术和术后非侵入性监测。我们的探针在主要器官中的最小积累提高了整体生物安全性。这项研究为新一代近红外 II 荧光团提供了一种简便的方法，并大大提高了小分子染料的亮度和药代动力学。
