利用亲脂性蛋白质口袋中菁染料 J-聚集体/单体平衡实现高效多步骤光疗:智能纳米诊疗的创新概念。
Exploiting cyanine dye J-aggregates/monomer equilibrium in hydrophobic protein pockets for efficient multi-step phototherapy: an innovative concept for smart nanotheranostics.
机构信息
Departamento de Química Orgánica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, IPQA, CONICET-UNC, Haya de la Torre y Medina Allende. Ciudad Universitaria, Córdoba, X5000 HUA, Argentina.
出版信息
Nanoscale. 2021 May 21;13(19):8909-8921. doi: 10.1039/d0nr09058a. Epub 2021 May 6.
After several decades of development in the field of near-infrared (NIR) dyes for photothermal therapy (PTT), indocyanine green (ICG) still remains the only FDA-approved NIR contrast agent. However, upon NIR light irradiation ICG can react with molecular oxygen to form reactive oxygen species and degrade the ICG core, losing the convenient dye properties. In this work, we introduce a new approach for expanding the application of ICG in nanotheranostics, which relies on the confinement of self-organized J-type aggregates in hydrophobic protein domains acting as monomer depots. Upon the fast photobleaching, while the dye is irradiated, this strategy permits the equilibrium-driven monomer replacement after each irradiation cycle that radically increases the systems' effectivity and applicability. Gadolinium-doped casein micelles were designed to prove this novel concept at the same time as endowing the nanosystems with further magnetic resonance imaging (MRI) ability for dual-modal imaging-guided PTT. By teaching a new trick to a very old dog, the clinical prospect of ICG will undoubtedly be boosted laying the foundation for novel therapeutics. It is anticipated that future research could be expanded to other relevant J-aggregates-forming cyanine dyes or nanocrystal formulations of poorly water-soluble photosensitizers.
经过近红外(NIR)染料在光热治疗(PTT)领域几十年的发展,吲哚菁绿(ICG)仍然是唯一获得 FDA 批准的 NIR 对比剂。然而,在近红外光照射下,ICG 会与分子氧反应生成活性氧物种,并降解 ICG 核心,失去方便的染料性质。在这项工作中,我们引入了一种扩展 ICG 在纳米治疗学中应用的新方法,该方法依赖于自组织 J 型聚集体在作为单体库的疏水性蛋白质结构域中的限制。在快速光漂白的同时,当染料被照射时,这种策略允许在每个辐照循环后进行平衡驱动的单体替换,这极大地提高了系统的效率和适用性。设计了镝掺杂的酪蛋白胶束来证明这一新颖的概念,同时赋予纳米系统进一步的磁共振成像(MRI)能力,用于双模式成像引导的 PTT。通过给一只非常老的狗一个新技巧,ICG 的临床前景无疑将得到提升,为新的治疗方法奠定基础。预计未来的研究可以扩展到其他相关的 J-聚集态形成的菁染料或疏水性光敏剂的纳米晶体制剂。