Heavy‐Atom‐Engineered Conjugated Polymer Enables Thermosensitized Synergistic Cancer Phototherapy

Abstract

Conjugated polymer‐based phototheranostics have attracted considerable attention for cancer treatment owing to their excellent photothermal properties and biocompatibility. However, integrating efficient photodynamic activity into conjugated polymer systems without compromising their intrinsic photothermal performance remains a major challenge. Here, we report structurally engineered selenophene‐doped polypyrrole nanoplatforms (Ppy‐PSe NPs) for imaging‐guided synergistic phototherapy. Incorporation of selenium‐containing heterocycles into the conjugated polypyrrole framework introduces a pronounced heavy‐atom effect, which promotes intersystem crossing and substantially enhances reactive oxygen species (ROS) generation while preserving broadband near‐infrared (NIR) absorption and efficient photothermal conversion. Upon NIR laser irradiation, Ppy‐PSe induces severe oxidative stress, lysosomal disruption, cytoskeletal collapse, and apoptotic cell death. Mechanistically, ROS‐mediated suppression of HSP90 disrupts the oncogenic JAK2/STAT3 signaling axis, thereby reprogramming tumor thermotolerance and sensitizing malignant cells to photothermal injury. In vivo, Ppy‐PSe exhibits favorable biosafety, efficient tumor accumulation, and robust photoacoustic imaging capability for real‐time therapeutic guidance. Notably, NIR‐triggered treatment achieves complete tumor eradication in a lymphoma xenograft model, particularly under NIR‐II irradiation. This work establishes a multifunctional conjugated polymer nanoplatform that integrates ROS amplification, thermo‐sensitization reprogramming, and imaging‐guided synergistic phototherapy for precision cancer treatment.