Extended π-Conjugated Bridge Strategy for an Enhanced Stokes Shift and Multimodal Imaging-Guided Type I/II Photodynamic Therapy Integrated With Photothermal Therapy

Abstract

Phototheranostics represent a pivotal modality for the concurrent diagnosis and treatment of malignant tumors. The development of high-performance phototheranostic agents has therefore become increasingly imperative. In this work, a “unity of a thousand blades” phototheranostic nanoplatform (TDTIC-M) with aggregation-induced emission (AIE) properties was synthesized through an extended electronic π-bridge strategy to enhance the Stokes shift and multimodal image-guided combined Type I/II photodynamic therapy and photothermal therapy (Type I/II PDT-PTT) synergistic phototherapy for breast cancer. Specifically, the target compounds (TIC-M, TTIC-M, and TDTIC-M) with donor-acceptor distorted conformations were prepared by a Knoevenagel coupling reaction. The TDTIC-M derivative, which incorporates two thiophene units as the π-bridge, boasts enhanced optical characteristics relative to both TIC-M and TTIC-M. This derivative was further encapsulated within DSPE-PEG₂₀₀₀ to form TDTIC-M nanoparticles (NPs) with good biocompatibility. Such NPs exhibit a large Stokes shift (∼270 nm), robust reactive oxygen species generation (¹O₂, ·OH, and ·O₂⁻), and a notable photothermal conversion efficiency (27.93%). Furthermore, TDTIC-M NPs demonstrate precise lysosome-targeted capacity and excellent phototherapy effects in vitro and effectively regulate the expression of apoptosis-related proteins (Caspase3, Bax, and Bcl-2). Moreover, TDTIC-M NPs demonstrate an exceptional multimodal imaging effect and synergistic phototherapy effect through integrating Type I/II PDT with PTT. Consequently, TDTIC-M emerges as a highly prospective phototheranostic candidate for multimodal imaging-guided cancer phototherapy.

Keywords

aggregation-induced emission / multimodal Imaging / phototheranostic / Type I/II PDT-PTT synergistic phototherapy

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