A “3+2” Cooperation Pattern of Amphipathic AIE Phototheranostic System for Multimodal Image‐Guided Synergistic Type I/II Photodynamic‐Photothermal Therapy

Phototheranostic agents (PTA) control the process of phototheranostics for cancer. However, the existing PTA still cannot meet the needs of practical biomedical applications. Hence the development of new PTA will be imperative. In this contribution, a "3+2" cooperation pattern of amphipathicity PTA (named TDTMSB) with aggregation-induced emission (AIE) features is designed and synthesized to perform near-infrared I/II fluorescence imaging, photoacoustic imaging, photothermal imaging, and Type I/II photodynamic therapy (PDT)-photothermal therapy (PTT) synergistic phototherapy for malignant tumors. Briefly, the target products (TMSB, TTMSB and TDTMSB) are successfully prepared by the reaction of 2-methyl-1-(3-sulfonatepropyl)-benzothiazolium (MSB) and triphenylamine derivatives. They have high rotor twisted structure, doner-acceptor (D-A) conformation and unique AIE performances. Compared to TMSB and TTMSB, the TDTMSB exhibits a long near infrared emission that extends into the NIR II region, large Stokes shift (300 nm) and small energy gap. Simultaneously, it shows high ROSs generation capacity (¹O₂, OH, and O₂ ^-), photothermal conversion efficiency (up to 40.5%), and specific recognition of lysosomes in tumor cells. Furthermore, TDTMSB not only exhibits excellent multimodal imaging capabilities, but also carry out Type I/II PDT-PTT synergistic enhancement effect for malignant tumor. Therefore, TDTMSB is expected to be a promising PTA for multimodal image-guided phototherapy of tumors.