Rationally Designed AIE Small Molecule Enabling NIR‑II Absorption and Multimodal Phototheranostics for Orthotopic Colon Cancer Treatment

Abstract

“One-for-all” phototheranostics, wherein a single-component molecule aggregate simultaneously integrates multiple optical imaging and therapeutic modalities, have emerged as highly attractive strategies for oncotherapy. Aggregation‑induced emission luminogens (AIEgens) have been proven to be ideal templates for developing such versatile systems, owing to their inherent superiority in finely balancing competing excited‑state energy dissipation pathways. Despite this significant advantage, achieving multimodal phototheranostic AIEgens with absorption in the second near‑infrared (NIR‑II, 1000–1700 nm) window remains a fundamental challenge, due to the intrinsic trade‑off between molecular planarity and twisting. Given the deep tissue penetration and high maximum permissible exposure associated with NIR‑II light, we herein constructed the first NIR‑II‑absorbing “one-for-all” phototheranostic AIEgen, named OTDTB, by concurrently harnessing the intrinsic versatility of AIEgens and leveraging donor–acceptor modulation, bond vibration, and alkyl chain engineering. Following formulation into nanoparticles (NPs), OTDTB NPs exhibit an emission peak at 1274 nm, satisfactory reactive oxygen species generation ability, and a high photothermal conversion efficiency of 71.5% under 1064 nm excitation. Coupled with excellent photostability and biosafety, OTDTB NPs well-performed in 1064 nm-excitable fluorescence–photoacoustic–photothermal trimodal imaging and synergistic photodynamic–photothermal therapy in colon cancer models. Overall, this work offers valuable design philosophy for constructing NIR‑II‑absorbing “one‑for‑all” phototheranostic platforms.