Electrostatic Reinforcement of NIR‐II Charge‐Transfer Complexes for Durable Phototheranostics

ABSTRACT Intermolecular charge‐transfer complexes (CTCs) are attractive for phototheranostics in the second near‐infrared window (NIR‐II) but suffer from intrinsic instability that undermines optical and therapeutic performance. Here, we introduce an electrostatic reinforcement‐based supramolecular strategy to construct a stable NIR‐II CTC, FBDFCTC nanoparticles (NPs), by co‐assembling the NIR‐II dye FBDF4NMe (donor) with 2,3,5,6‐tetrafluoro‐7,7,8,8‐tetracyanoquinodimethane (F 4 TCNQ, acceptor) at a ratio of 1:2. The resulting FBDFCTC NPs feature intense NIR‐II absorption ( ε 1064 nm = 1.73 × 10 4 M −1 cm −1 ) and exceptional photothermal conversion efficiency ( η = 56.3%) under 1064 nm irradiation. Beyond efficient photothermal therapy (PTT), the strong electrophilicity of F 4 TCNQ enables selective depletion of intracellular glutathione and cysteine, thereby amplifying oxidative stress and triggering exogenous iron‐free ferroptosis. Notably, unlike conventional CTCs, FBDFCTC NPs retain robust NIR‐II photothermal activity even after partial CTC dissociation, ensuring durable therapeutic performance in tumor environments. In vivo, FBDFCTC NPs afford high‐contrast NIR‐II photoacoustic imaging (PAI) for precise tumor localization and vascular mapping, followed by PAI‐guided photothermal ablation. This work establishes electrostatic reinforcement of CTCs as a generalizable paradigm to achieve multifunctional NIR‐II platforms that integrate deep‐tissue PTT with tumor microenvironment modulation, opening new avenues for precise, durable, and safe cancer therapy.