Molecularly manipulating pyrazinoquinoxaline derivatives to construct NIR-II AIEgens for multimodal phototheranostics of breast cancer bone metastases

Ping Zheng; Xueke Yan; Jun Zhu; Yi Liu; Lei Wang; Huifang Su; Dong Wang; Ben Zhong Tang

doi:10.1016/j.biomaterials.2025.123105

Molecularly manipulating pyrazinoquinoxaline derivatives to construct NIR-II AIEgens for multimodal phototheranostics of breast cancer bone metastases

Biomaterials. 2025 Jan 11:317:123105. doi: 10.1016/j.biomaterials.2025.123105. Online ahead of print.

Authors

Ping Zheng¹, Xueke Yan², Jun Zhu³, Yi Liu³, Lei Wang¹, Huifang Su⁴, Dong Wang⁵, Ben Zhong Tang⁶

Affiliations

¹ Center for AIE Research, Guangdong Provincial Key Laboratory of New Energy Materials Service Safety, College of Materials Science and Engineering, Shenzhen University, Shenzhen, 518060, China; College of Physics and Optoelectronic Engineering, Shenzhen University, Shenzhen, 518060, China.
² Department of Orthopaedic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
³ Center for AIE Research, Guangdong Provincial Key Laboratory of New Energy Materials Service Safety, College of Materials Science and Engineering, Shenzhen University, Shenzhen, 518060, China.
⁴ Department of Orthopaedic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China. Electronic address: [email protected].
⁵ Center for AIE Research, Guangdong Provincial Key Laboratory of New Energy Materials Service Safety, College of Materials Science and Engineering, Shenzhen University, Shenzhen, 518060, China. Electronic address: [email protected].
⁶ Center for AIE Research, Guangdong Provincial Key Laboratory of New Energy Materials Service Safety, College of Materials Science and Engineering, Shenzhen University, Shenzhen, 518060, China; School of Science and Engineering, Shenzhen Institute of Aggregate Science and Technology, The Chinese University of Hong Kong, Shenzhen (CUHK-Shenzhen), Guangdong, 518172, China. Electronic address: [email protected].

PMID: 39818143
DOI: 10.1016/j.biomaterials.2025.123105

Abstract

Multimodal phototheranostics on the basis of single molecular species shows inexhaustible and vigorous vitality, particularly those emit fluorescence in the second near-infrared window (NIR-II), the construction of such exceptional molecules nonetheless retains formidably challenging. In view of the undiversified molecular skeletons and insufficient phototheranostic outputs of previously reported NIR-II fluorophores, herein, electron acceptor engineering based on heteroatom-inserted rigid-planar pyrazinoquinoxaline was manipulated to fabricate aggregation-induced emission (AIE)-featured NIR-II counterparts with donor-acceptor-donor (D-A-D) architecture. Systematical investigations substantiated that one of those synthesized AIE molecules, namely 4TPQ, incorporating a fused thiophene acceptor, synchronously exhibited high molar absorptivity (ε), NIR-II emission, typical AIE tendency, significant reactive oxygen species (ROS) generation, and high photothermal conversion efficiency. These extraordinary behaviors endowed 4TPQ nanoparticles with unprecedented performance on NIR-II fluorescence/photothermal imaging-navigated synergistic photodynamic/photothermal inhibition of tumors, as confirmed by the mice model of breast cancer bone metastases. This study thus brings significant insights into developing phototheranostic systems for clinical trials.

Keywords: Acceptor engineering; Aggregation-induced emission; Breast cancer bone metastases; NIR-II emission; Versatile phototheranostics.