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 (D₂) as the optimal electron donor through a systematic screening against a TFTQ acceptor. Significantly, the 2A-D₂ 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-D₂ 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.

Keywords

charge-transfer complexes / donor screening / NIR-II phototherapy / stoichiometry engineering

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2026 The Author(s). Aggregate published by SCUT, AIEI, and John Wiley & Sons Australia, Ltd.