Chimie ParisTech, PSL University, CNRS , Institute of Chemistry for Life and Health Sciences, Laboratory for Inorganic Chemical Biology , 75005 Paris , France.
Department of Chemistry , University of Zurich , Winterthurerstrasse 190 , CH-8057 Zurich , Switzerland.
Inorg Chem. 2019 Sep 16;58(18):12422-12432. doi: 10.1021/acs.inorgchem.9b02019. Epub 2019 Sep 4.
Fluorescence imaging is a powerful tool in biomedical research. It has been frequently used to uncover or better understand physiological mechanisms in disease-related processes such as cancer. The majority of chromophores used for imaging are based on a 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) scaffold. However, their applications are limited due to their poor water solubility as well as poor cancer cell selectivity. To circumvent these drawbacks, we present herein the use of bis(dipyrrinato)zinc(II) complexes. As this class of compounds is associated with a quenching effect of the excited state in water, the lead compound of this study () was encapsulated in a polymer matrix with biotin as a targeting moiety (). This encapsulation improved the water solubility, overcame the quenching effects in water, as well as allowed selective accumulation in the lysosomes with a bright fluorescence signal in monolayer cells as well as 3D multicellular tumor spheroids (MCTS). As a benefit from the biotin targeting moiety, the nanoparticles were majorly taken up by the sodium dependent multivitamin transporter (SMVT) which is overexpressed in various cancers cells and selectively accumulated in cancerous cells over noncancerous cells.
荧光成像是生物医学研究中一种强大的工具。它已被广泛用于揭示或更好地理解与疾病相关过程中的生理机制，如癌症。大多数用于成像的发色团基于 4,4-二氟-4-硼-3a,4a-二氮杂-s-茚（BODIPY）支架。然而，由于其较差的水溶性以及对癌细胞的选择性较差，它们的应用受到限制。为了克服这些缺点，我们在此提出使用双（二吡咯甲川）锌（II）配合物。由于这类化合物与水中激发态的猝灭效应有关，本研究的先导化合物（）被包封在聚合物基质中，生物素作为靶向部分（）。这种封装提高了水溶性，克服了水中的猝灭效应，并允许在单层细胞以及 3D 多细胞肿瘤球体（MCTS）中选择性地在溶酶体中积累，产生明亮的荧光信号。由于生物素靶向部分的作用，纳米颗粒主要被钠依赖性多种维生素转运体（SMVT）摄取，SMVT 在各种癌细胞中过度表达，并在癌细胞中选择性积累，而在非癌细胞中则不会积累。
