Dual-responsive semiconducting oligomer/doxorubicin nanoplatform for photoacoustic imaging-guided synergistic chemo-photothermal therapy

Effective image-guided and precisely controlled drug release remains a critical challenge in cancer therapy, particularly for overcoming drug resistance and minimizing systemic toxicity. Herein, we developed a multifunctional nanoplatform by co-encapsulating a newly engineered near-infrared (NIR)-absorbing semiconducting oligomer (TD19) and doxorubicin (DOX) into DSPE-PEG₅₀₀₀ carriers. Benefiting from a donor-acceptor molecular design, TD19 exhibited a high extinction coefficient, extended π-conjugation, and superior photothermal conversion efficiency, which directly contributed to strong photoacoustic imaging (PAI) and photothermal therapy (PTT) performance. The resulting TD19/DOX nanoparticles (TD19/DOX-NPs) demonstrated dual-responsive drug release triggered by 808 nm laser irradiation and the acidic tumor microenvironment. In vitro, the nanoplatform enhanced cellular uptake, nuclear delivery of DOX, and synergistic apoptosis of breast cancer cells. In vivo, TD19/DOX-NPs achieved precise PAI-guided tumor localization, efficient tumor ablation (96.8% growth inhibition), and no observable acute systemic toxicity in the 4T1 mouse model. This study highlights the structure-function-therapeutic relationship of the designed semiconducting oligomer, linking its rational molecular engineering to chemo-photothermal synergy as a promising nanotheranostic candidate for breast cancer precision therapy.