Li Heng, Li Qian, Guo Luying, Guo Xing, Zhang Qi, Wang Zhaoyun, Wu Qinghua, Wang Shaozhen, Jiao Lijuan, Hao Erhong
Key Laboratory of Functional Molecular Solids, Ministry of Education, Anhui Province Key Laboratory of Biomedical Materials and Chemical Measurement, School of Chemistry and Materials Science, Anhui Normal University, Wuhu 241002, China.
School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China.
J Am Chem Soc. 2025 Sep 3;147(35):31900-31910. doi: 10.1021/jacs.5c09606. Epub 2025 Jul 26.
The photocage, an advanced platform for drug delivery and photoactivation imaging, has attracted wide attention in biomedicine. Despite recent advancements in shifting irradiation wavelengths to visible and near-infrared light, improving photolysis quantum yield and the corresponding uncaging cross section, key parameters for efficient photocages, remains highly challenging. Here, we address this challenge by introducing light-controlled COO-B bond cleavage from tetracoordinate boron linked to dipyrrin, aryl, and carboxylic acid groups. We developed a multicomponent diversity-oriented one-pot method to streamline the synthesis of BODIPY-cages, enabling the creation of a diverse library of photocages for systematic investigation of their photorelease structure-activity relationships and mechanisms. Thanks to efficient COO-B bond photolysis and the impressive extinction coefficients of BODIPYs, the developed photocages possess uncaging cross sections up to 1488 M cm, enabling rapid lysosome photoactivation fluorescence imaging at low light and dye doses (0.2 mW, 50 nM) and sequential two-photon (λ = 950 nm) photoactivation in zebrafish. When loaded with the drug valproic acid (), these photocages optimize drug uptake and achieve precise photoactivation release in the endoplasmic reticulum or lysosomes, boosting drug efficacy ∼18,540-fold. Our one-pot accessed photocages, with impressive uncaging cross sections, two-photon activation capability, and photoactivatable fluorescence imaging and drug release abilities, provide a valuable paradigm for developing multifunctional photoactivation platform. We expect our study to break new ground in the construction of tetracoordinate boron photocages with diverse structures and functions.
光笼作为一种用于药物递送和光激活成像的先进平台，在生物医学领域引起了广泛关注。尽管最近在将照射波长转移到可见光和近红外光、提高光解量子产率以及相应的解笼截面（高效光笼的关键参数）方面取得了进展，但仍然极具挑战性。在此，我们通过引入与二吡咯、芳基和羧酸基团相连的四配位硼的光控COO - B键断裂来应对这一挑战。我们开发了一种多组分多样性导向的一锅法来简化BODIPY - 笼的合成，从而能够创建一个多样化的光笼库，用于系统研究其光释放结构 - 活性关系和机制。由于高效的COO - B键光解以及BODIPY令人印象深刻的消光系数，所开发的光笼具有高达1488 M cm的解笼截面，能够在低光和低染料剂量（0.2 mW，50 nM）下进行快速溶酶体光激活荧光成像，并在斑马鱼中进行顺序双光子（λ = 950 nm）光激活。当装载药物丙戊酸（）时，这些光笼优化了药物摄取，并在内质网或溶酶体中实现了精确的光激活释放，使药物功效提高了约18540倍。我们通过一锅法获得的光笼具有令人印象深刻的解笼截面、双光子激活能力以及光激活荧光成像和药物释放能力，为开发多功能光激活平台提供了有价值的范例。我们期望我们的研究在构建具有多样结构和功能的四配位硼光笼方面开辟新的道路。
