State Key Laboratory of Supramolecular Structure and Materials, Center for Supramolecular Chemical Biology, College of Chemistry, Jilin University, Changchun, 130012, P. R. China.
Joint Laboratory of Opto-Functional Theranostics in Medicine and Chemistry, The First Hospital of Jilin University, Changchun, 130021, P. R. China.
Adv Mater. 2023 Nov;35(46):e2306773. doi: 10.1002/adma.202306773. Epub 2023 Oct 15.
Despite the wide range of applications of bright NIR-II polymethine scaffolds in biomedical imaging, their solvatochromism and aggregation-caused quenching (ACQ) effects in aqueous solutions limit their inherent brightness using traditional encapsulation methods, and effective hydrophilization strategies are still scarce. Here, a new set of Flav dyes is synthesized and PEGylated, followed by manufacturing DSPE@FlavP nanoparticles using a self-adaptive co-assembly strategy to overcome these limitations. FlavP can autonomously adjust its conformation when co-assembled with DSPE-PEG , resulting in high-efficiency luminescence (≈44.9% fluorescence of Flav in DMSO). DSPE@FlavP enables NIR-IIb (>1500 nm) angiography with high signal-to-noise ratios. Notably, this co-assembly can occur in situ between FlavP with proteins in the living body based on a novel mechanism of brightness activation induced by disassembly (BAD), achieving consistent brightness as DSPE@FlavP in blood or serum. The self-adaptive co-assembly strategy can be enhanced by incorporating an IPA moiety, which dynamically binds to albumin to prolong the dye's blood circulation time. Thus, the "enhanced" BAD is successfully applied to long-term vascular imaging and sciatic nerve imaging. Both the self-adaptive co-assembly strategy and BAD phenomenon improve the selectivity and availability of the hydrophilization methods, paving the way for efficient biological applications of polymethine dyes.
尽管高亮近红外二区（NIR-II）聚甲川染料在生物医学成像中有广泛的应用，但它们在水溶液中的溶剂化变色和聚集猝灭（ACQ）效应限制了其使用传统封装方法的固有亮度，并且有效的亲水策略仍然稀缺。在这里，我们合成并聚乙二醇化了一组新的 Flav 染料，然后使用自适应共组装策略制造了 DSPE@FlavP 纳米颗粒，以克服这些限制。FlavP 与 DSPE-PEG 共组装时可以自动调整其构象，从而实现高效率的发光（≈DMSO 中 Flav 的 44.9%荧光）。DSPE@FlavP 能够实现 NIR-IIb（>1500nm）血管造影，具有高信噪比。值得注意的是，这种共组装可以基于一种通过解组装（BAD）诱导的亮度激活的新机制，在体内的 FlavP 与蛋白质之间原位发生，从而在血液或血清中实现与 DSPE@FlavP 一致的亮度。通过引入 IPA 部分可以增强自适应共组装策略，IPA 部分可以动态结合白蛋白以延长染料的血液循环时间。因此，“增强”的 BAD 成功应用于长期血管成像和坐骨神经成像。自适应共组装策略和 BAD 现象都提高了亲水方法的选择性和可用性，为聚甲川染料的有效生物应用铺平了道路。
