Donor Screening and Stoichiometry Engineering‐Driven Supramolecular Charge‐Transfer Complexes for Synergistic Tumor Near‐Infrared‐II Phototherapy

ABSTRACT

The advancement of organic near‐infrared‐II (NIR‐II) photothermal agents is impeded by complex structural designs and arduous synthetic procedures. While supramolecular charge‐transfer complexes (CTCs) offer a facile assembly route, efficient NIR‐II‐absorbing CTCs remain scarce. Crucially, a fundamental paradox arises: tight planar stacking for narrow‐bandgap NIR‐II absorption inevitably induces severe aggregation‐caused quenching (ACQ), suppressing reactive oxygen species generation and disabling synergistic photothermal/photodynamic therapy. Herein, we identified DBTTF (D ₂ ) as the optimal electron donor through a systematic screening against a TFTQ acceptor. Significantly, the 2A‐D ₂ assembly with a 2‐to‐1 acceptor‐to‐donor ratio was established as the optimal candidate due to its highest molar extinction coefficient by deciphering the stoichiometry‐property relationship. Molecular dynamics simulations revealed that this acceptor‐rich environment induces looser molecular packing and weaker intermolecular interactions. This unique configuration successfully resolved the ACQ bottleneck, enabling efficient reactive oxygen species generation while maintaining a high photothermal conversion efficiency of 40.3%. Driven by these synergetic effects, 2A‐D ₂ induced severe mitochondrial dysfunction and DNA damage under 1064 nm irradiation, achieving robust 94.5% tumor inhibition and suppressing pulmonary metastasis. Thus, this study established a robust framework for developing advanced NIR‐II CTCs by integrating donor screening with precise stoichiometric engineering to harmonize photothermal and photodynamic modalities for tumor ablation.