Kinetically Gated and Self-Limiting Crystallization Enables Allosteric Phototheranostic Nanocrystals

Crystalline organic nanomaterials with programmable photophysical functions hold great promise for precision medicine, however, achieving controlled crystallization and responsive activation remains challenging. Here we report a kinetically gated and self-limiting crystallization (KGSLC) strategy for constructing allosteric phototheranostic nanocrystals. Through rational molecular design, the TCF acceptor unit governs intrinsic size confinement via surface hydration, while the hydroxyl group directs hydrogen-bond-assisted π-π stacking to promote highly crystalline assemblies. The resulting HICyT nanocrystals (HICyT NCs) exhibit strong near-infrared absorption, dual-type reactive oxygen species generation, and catalase-like activity. A disulfide-bridged prodrug, (HICyT)₂S, further encodes tumor microenvironment-triggered activation, converting into active HICyT NCs upon glutathione cleavage. The resulting nanocrystals enable deep-tissue penetration, bright albumin-activated NIR-I/II fluorescence, and potent in vivo tumor ablation under irradiation. This kinetically programmed crystallization integrates structural precision, spatiotemporal activation, and real-time imaging into a single organic platform, offering a promising route toward self-reporting phototheranostic materials.