Nanomaterials for In Vivo Photoacoustic Sensing: Emerging Strategies and Future Outlook

Photoacoustic imaging has emerged as a powerful modality for noninvasive, high-resolution visualization of deep tissues. The integration of smart nanomaterials is now extending PAI beyond structural imaging into functional and molecular sensing. In this perspective, we highlight recent advances in the design of stimuli-responsive nanomaterials tailored for in vivo applications, with emphasis on targeting strategies, operation in the NIR-II Window, and sensing specificity. We compare always-on versus activatable probes, summarize key molecular and microenvironmental targets such as pH, reactive oxygen species, metal ions, and enzymes, and discuss how these platforms report on disease progression and therapeutic response. We also outline emerging directions including NIR-II photoacoustic nanomaterials, PAI-guided theranostic probes, and translational pathways from chemistry to the clinic. Together, these innovations are positioning nanomaterial-enabled photoacoustic sensing as a cornerstone technology for precision diagnostics and image-guided therapy in clinical.