Controlling Conjugated Polymer Assembly from Parallel to Intersecting Backbone Stacking for Enhanced Charge Separation and Efficient Photodynamic Therapy

Aqueous organic semiconductor nanoparticles (OSNPs) are widely investigated for energy and biomedical applications, such as photocatalytic hydrogen production, carbon dioxide conversion, and photothermal or photodynamic cancer therapies. A critical factor governing their performance is the charge separation efficiency. Although conventional strategies focus on varying donor-acceptor combinations or blending ratios, we report a distinct approach by controlling the molecular assembly structure of conjugated polymers, shifting from a parallel to an intersecting backbone stacking mode. Multiscale simulations demonstrated that this structural modulation regulates macroscopic phase separation and local molecular packing, yielding OSNPs with reduced average size and enhanced structural uniformity. Spectroscopic analysis revealed that the intersecting assembly successfully induces significant photoluminescence quenching, extended charge-separation lifetimes, and accelerated charge-transfer kinetics.
Under near-infrared (NIR) irradiation, this optimized morphology enabled an efficient water-oxidation-based photodynamic therapy (PDT) mechanism using H2O as an electron donor, quantitatively enhancing the generation of specific reactive oxygen species (ROS), including singlet oxygen and hydroxyl radicals. In vitro and in vivo evaluations verified that the intersecting nanoparticles exhibit exceptional cancer cell cytotoxicity and tumor suppression. Furthermore, the induction of immunogenic cell death (ICD) via this enhanced PDT triggered a potent synergistic anti-tumor immune response when combined with immune checkpoint inhibitors, offering a powerful platform for advanced biomaterials and nanomedicine.