Xin Xie,1,2,* Jie Zeng,1,2,* Miao-Yan Xu,1,2 Xin-Hao Han,1 Bing Fan,3 Xianglong Li,4 Duo-Duo Wei,1,2 Xiao-Jian Han,1,5 Shaorong Huang1 

1Institute of Geriatrics, Jiangxi Provincial People’s Hospital, the First Affiliated Hospital of Nanchang Medical College, Nanchang, Jiangxi, 330006, People’s Republic of China; 2School of Pharmacy, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China; 3Department of Radiology, Jiangxi Provincial People’s Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, Jiangxi, 330006, People’s Republic of China; 4Jiangxi Key Laboratory of Organic Chemistry, Institute of Organic Chemistry, Jiangxi Science & Technology Normal University, Nanchang, 330013, People’s Republic of China; 5The Second Department of Neurology, Jiangxi Provincial People’s Hospital, the First Affiliated Hospital of Nanchang Medical College, Nanchang, Jiangxi, 330006, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Xiao-Jian Han; Shaorong Huang, Email hanxiaojian@hotmail.com; huangshaorong@ncmc.edu.cn

Background: The exploration of non-symmetric compound for combined photothermal therapy (PTT) and photodynamic therapy (PDT) in tumor treatment remains largely unexplored.
Methods: Through a molecular design strategy, a series of compound (Y-4Cl, Y-2Br, and Y-2Cl-Br) with fused - ring benzothiazole - pyrrole - thiophene - indenone constructure were synthesized to explore its phototherapy properties, to investigate their phototherapeutic properties, respectively. The non-symmetric compound Y-2Cl-Br was further formulated into nanoparticles (NPs) for detailed evaluation.
Results: The non-symmetric organic compound Y-2Cl-Br demonstrated a high molar extinction coefficient (ϵ) of 3.0 × 105 M⁻¹ cm⁻¹. Y-2Cl-Br NPs exhibited exceptional photothermal performance, including a temperature increase (ΔT) of 34 °C and a photothermal conversion efficiency (PCE) of 61.2%. Additionally, Y-2Cl-Br NPs displayed superior photostability, a reactive oxygen species (ROS) generation efficiency 9.8-fold higher than indocyanine green (ICG), remarkable fluorescence imaging (FLI) capabilities, and excellent biocompatibility.
Conclusion: Both in vitro and in vivo studies confirmed that Y-2Cl-Br NPs are highly effective in PTT and PDT for tumor treatment, with minimal adverse effects. This work provides valuable insights into the design and application of non-symmetric organic compound photosensitizers (PSs) in cancer therapy.

Keywords: non-symmetric organic compound, photodynamic therapy, photothermal therapy, tumor