Mitochondria-targeted aggregation induced emission theranostics: crucial importance of activation

• Published in: Chemical science (Cambridge) 2016-08, Vol.7 (9), p.65-659
• Main Authors: Shin, Weon Sup, Lee, Min-Goo, Verwilst, Peter, Lee, Joung Hae, Chi, Sung-Gil, Kim, Jong Seung
• Format: Article
• ISSN: 2041-6520; 2041-6539
• DOI: 10.1039/c6sc02236g

Tissue selective targeting and specific suborganellular localization combined with an efficient pathology associated enzymatic activation of drugs in drug delivery systems may exhibit a clear advantage over conventional cancer treatment. Here, a mitochondria targeted aggregation induced emission (AIE) fluorophore further conjugated with an NAD(P)H:quinone oxidoreductase-1 (NQO1) cleavable masking unit showed preferential uptake in cancer cells and was selectively activated, resulting in bright AIE fluorescence and apoptosis via the caspase pathway, triggered by mitochondrial dysfunction. In vivo experimental data further support the conclusions from in vitro experiments, clearly showing the dependence of the therapy's success on both the suborganelle localization and specific in situ activation. And the site specific and enzyme dependent activation and aggregation was further supported by in vivo and ex vivo imaging. As a whole, the data comprised in this work represent a strong argument for the further development of this type of novel anticancer drugs. A mitochondria targeted AIE fluorophore was further decorated with an NQO1 cleavable masking unit and showed selective targeting to and activation in cancer cells resulting in bright AIE fluorescence and apoptosis triggered by mitochondrial dysfunction.