Nitric Oxide Conjugation Transforms NIR‐II AIEgens Into Potent Hypoxia‐Tolerant Type I Photosensitizers
Abstract
ABSTRACT Near‐infrared (NIR)‐activated type I photosensitizers (PSs) with aggregation‐induced emission (AIE) properties are highly attractive for photodynamic therapy (PDT) of deep‐seated and inoperable tumors. However, most NIR‐activated AIEgens, especially donor–acceptor–donor (D‐A‐D) benzobisthiadiazole derivatives, are mainly used for bioimaging and photothermal therapy due to their intrinsically small S 1 →S 0 energy gaps (Δ E S1‐S0 ) severely limiting reactive oxygen species (ROS) generation. Here, we present a strategy to convert widely adopted D‐A‐D NIR‐activated AIEgens into NIR‐activated type I PSs by conjugating nitric oxide (NO) to the electron‐donating units. Upon NO conjugation, the resulting compounds NO‐T‐TQT and NO‐2TT‐ o C6B become efficient generators of NIR‐activated hydroxyl radical (•OH), exhibiting a 13.2‐fold and 5.4‐fold increase in superoxide (O 2 •− ) production compared with their parent molecules, respectively. In contrast, T‐TQT, 2TT‐ o C6B, and related analogues produce negligible ROS and no detectable •OH. Mechanistic studies reveal that NO conjugation narrows the singlet‐triplet energy gap, strengthens spin‐orbit coupling to enhance intersystem crossing, optimizes redox potentials to favor electron transfer, and lowering hydrogen atom affinity. NO‐2TT‐ o C6B nanoparticles achieved potent in vitro cytotoxicity and effective in vivo tumor ablation under NIR irradiation. This work establishes a general approach to transform conventional NIR‐activated D‐A‐D AIEgens into high‐performance type I PSs, significantly advancing their clinical potential in PDT.
Article Details
Authors (12)
Junjun Ni
Yan Feng
Jianquan Zhang
Guangdong Basic Research Center of Excellence for Aggregate Science, School of Science and Engineering
Muhammad Muazzam Naseer
Bioinspired Engineering and Biomechanics Center (BEBC) School of Life Science and Technology The Key Laboratory of Biomedical Information Engineering of Ministry of Education Xi'an Jiaotong University Xi'an P. R. China
Liang Guo
Department of Chemistry
Kunpeng Feng
Bioinspired Engineering and Biomechanics Center (BEBC) School of Life Science and Technology The Key Laboratory of Biomedical Information Engineering of Ministry of Education Xi'an Jiaotong University Xi'an P. R. China
Ryan T. K. Kwok
Department of Chemistry, the Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction, Department of Chemical and Biological Engineering, State Key Laboratory of Nervous System Disorders, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR 999077, China
Jacky W. Y. Lam
Department of Chemistry, the Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction, Department of Chemical and Biological Engineering, State Key Laboratory of Nervous System Disorders, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR 999077, China
Lianrui Hu
Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, Shanghai Frontiers Science Center of Molecule Intelligent Syntheses, School of Chemistry and Molecular Engineering
Xiaoran Yin
Department of Oncology The Second Affiliated Hospital of Xi'an Jiaotong University Xi'an P. R. China
Guorui Jin
Bioinspired Engineering and Biomechanics Center (BEBC) School of Life Science and Technology The Key Laboratory of Biomedical Information Engineering of Ministry of Education Xi'an Jiaotong University Xi'an P. R. China
Ben Zhong Tang
School of Science and Engineering, Guangdong Basic Research Center of Excellence for Aggregate Science, The Chinese University of Hong Kong (Shenzhen), Longgang, Shenzhen 518172, Guangdong, P. R. China