A Strategy to Design Non-Symmetric Compound by Modifying the End-Group Functional Atoms for Photothermal and Photodynamic Therapy of Tumor.

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.