Decoupling Optical Functions via Ratio-Tunable Conjugated Copolymers with Hydrogen-Bond-Enforced Rigidity for Quenching-Resistant NIR-II Phototheranostics.

Abstract

Organic near-infrared II (NIR-II) phototheranostic agents hold great promise for tumor imaging and phototherapy. However, their development is fundamentally challenged by the coupled and competing optical pathways in conventional designs: rigid planar fluorophores that excel in the molecular state often suffer from severe aggregation-caused quenching (ACQ) in nanoparticles, leading to drastic losses in both fluorescence and reactive oxygen species (ROS) generation. To decouple these optical functions, we report a modular copolymer-based anti-quenching strategy by integrating a flexible segment with a hydrogen-bond-enforced rigid segment. The key to decoupling lies in the tunable segment ratio, which allows composition-dependent modulation with reduced trade-offs of NIR-II fluorescence, ROS production, and photothermal conversion. As the rigid-segment fraction increases in the copolymer series (F8R2, F5R5, and F2R8), NIR-II fluorescence and ROS generation are markedly enhanced, while the photothermal conversion efficiency is only slightly compromised. Remarkably, the F2R8 nanoparticles (80% rigid segment) retain >60% of their NIR-II fluorescence and high ROS productivity in the aggregated state, starkly contrasting the >90% quenching observed in conventional ACQ-type small molecules. This effective partial decoupling of optical functions and suppression of ACQ enable high-contrast NIR-II fluorescence imaging-guided combined phototherapy <i>in vivo</i>. Our work provides a general design paradigm based on copolymer modularity for developing high-performance quenching-resistant organic phototheranostics.