Organic NIR-II Dyes with Ultralong Circulation Persistence for Image-guided Delivery and Therapy

Yang Li, Jianfeng Gao, Shuping Wang, Shijun Li, Xiaowen Hou, Yanna Pan, Jialu Gao, Xue Qiao, Zhiquan Tian, Deliang Chen, Hai Deng, Zixin Deng, Xuechuan Hong, Yuling Xiao

Journal of Controlled Release 2022， 342，157-169

https://doi.org/10.1016/j.jconrel.2022.01.005

Abstract

Nanocarriers hold great promise for the controlled release of therapeutic payloads to target organs/tissues and extended duration of anticancer agents in the bloodstream. However, limited data on their in vivo pharmacokinetics and delivery process hamper clinical applications. Here we report a series of micellar nanocarriers self-assembled from new-generation thiophenthiadiazole (TTD)-based NIR-II fluorophores HLAnP (n = 1–4) for simultaneous bioimaging and drug delivery. The NIR-II HLA4P nanocarrier displays exceptional non-fouling performance, minimal immunogenicity, ultralong blood half-life, and high tumor accumulation even with different administration routes. When used as a drug carrier, HLA4P with encapsulated doxorubicin (DOX) realized accurate tumor targeting and continuous real-time in vivo NIR-II tracking of drug delivery and therapy, showing a sustained release rate, improved therapeutic effect, and diminished cardiotoxicity as compared to free DOX. This study provides a new perspective on the design of dual-functional NIR-II fluorophores for diagnostic and therapeutic applications.