Benzothiadiazole-Based Donor–Acceptor Nanoparticles With Enhanced Reactive Oxygen Species (ROS) Under One- and Two-Photon Excitation as Promising Photosensitizers

Abstract

Photodynamic therapy (PDT) is a clinically promising cancer treatment modality due to its precise spatial and temporal control and minimal systemic toxicity. However, developing photosensitizers (PSs) that achieve efficient reactive oxygen species (ROS) generation under both one-photon (1P) and two-photon (2P) excitation remains a major challenge. This study reports benzothiadiazole (BTD)-based tri-substituted chromophores incorporating either phenyl or triphenylamine (TPA) as the central donor unit and phenothiazine (PTZ) at the periphery were formulated into stable nanoparticles (NPs). The nanoencapsulation markedly enhanced ROS generation efficiency, as evidenced by accelerated degradation of 1,3-diphenylisobenzofuran (DPBF). BTD-T1 NPs produced a 55-fold higher ROS generation compared to BTD-T1. The TPA-substituted BTD NPs exhibited high ROS generation under both 525 nm continuous-wave 1P and 800 nm/1000 nm femtosecond-pulsed 2P excitation. Collectively, these results show that nanoencapsulation markedly enhances the aqueous stability, dispersibility, and photophysical performance of BTD chromophores. The heavy atom-free BTD NPs exhibit enhanced ROS generation and dual 1P/2P activity, offering a promising photosensitizer. © 2026 Wiley-VCH GmbH.