From materials to medicine: formulation-driven optimization and clinical prospects of NIR-II optical imaging agents

Conventional optical imaging is constrained by photon absorption and multiple scattering in biological tissues. Extending excitation and emission into the second near-infrared window (NIR-II, 1000-1700 nm) markedly suppresses tissue autofluorescence and improves imaging fidelity. However, enhanced optical performance alone does not ensure clinical translatability. In this review, we distinguish the conceptual boundary between optical probes and translational optical agents, highlighting the critical role of formulation engineering in bridging material functionality with biomedical applicability. Representative NIR-II probe classes are summarized together with their intrinsic advantages and translational limitations. We further discuss key formulation strategies for optical agent construction, including targeting engineering, hydrophilicity regulation, size optimization, and carrier-assisted integration. Recent advances in cardiovascular, oncological, neurological, and multimodal imaging applications are also reviewed. Finally, remaining challenges related to biosafety, imaging hardware, and clinical standardization are discussed. By adopting a formulation-centered perspective, this review emphasizes the transition from signal-generating probes to clinically relevant optical agents and outlines future directions for accelerating the translation of NIR-II imaging toward precision diagnostics and image-guided medicine.