Zhenghui Li,1– 3,* Xufei Bian,1,* Huiyu Wu,1 Ling He,1 Zuhua Zeng,1 Lei Zhong,1 Yao Liu,1 Yu Li,1 Guihao Hu,1 Fanglin Mi,2 Zhen Liu,2 Jiang Zhu1 

1Medical Imaging Key Laboratory of Sichuan Province, North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China; 2Department of Stomatology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China; 3Beijing Anzhen Nanchong Hospital, Capital Medical University & Nanchong Central Hospital, Nanchong, Sichuan, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Zhen Liu, Department of Stomatology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, 637100, People’s Republic of China, Email 18157645@qq.com Jiang Zhu, Medical Imaging Key Laboratory of Sichuan Province, North Sichuan Medical College, Nanchong, Sichuan, 637000, People’s Republic of China, Email zhujiang@nsmc.edu.cn

Purpose: Phototherapy have gained significant traction in the treatment of tumors. However, the successful implementation of these therapies relies on photosensitizers with superior properties and precise guidance mechanisms.
Methods: In this study, we introduce an innovative method for the surface modification of titanium dioxide (TiO2) nanoparticles through HRP-catalyzed covalent incorporation of Mn(II) chelate (Mn-Dopa) and dopamine.
Results: This modification extends TiO2 nanoparticels’ light absorption from ultraviolet to the near-infrared (NIR) range, endowing the nanoparticles with MRI-guided phototherapy capabilities. The resulting nanotheranostics system, TiO2@PDA-MnDopa, demonstrated over 5-fold enhanced relaxivity compared to the monomeric MnDopa and exhibited synergistic phototherapy effects upon 808 nm laser excitation, with a photothermal conversion efficiency of 15.91%. In vitro and in vivo pharmacodynamics studies showed that the TiO2@PDA-MnDopa demonstrated good safety in the HSC3 cell line and corresponding tumor-bearing mice, while effectively inhibiting tumor growth under 808 nm laser excitation.
Conclusion: This multifunctional nanotheranostic, integrating high relaxivity with synergistic PTT/PDT for MR imaging-guided phototherapy, holds great potential for applications in the early diagnosis, noninvasive treatment, and prognostic evaluation of oral squamous cell carcinoma.

Keywords: photodynamic therapy, photothermal therapy, oral squamous cell carcinoma, titanium dioxide, horseradish peroxidase catalysis