NIR‐II Dual‐Modal Photoacoustic and OCT/OCTA Contrast Mechanisms Imaging Microenvironment Responses for Precision‐Guiding Tumor Photothermal Theranostics

Abstract Non‐invasive, 3D visualization and quantification of dynamic molecular events within the tumor microenvironment are critical for advancing cancer theranostics. However, integrating high‐resolution anatomical imaging with functional hemodynamic and vascular assessments remains challenging. Consequently, how photothermal therapy (PTT) differentially influences microenvironmental responses during treatment‐particularly in the second near‐infrared window (NIR‐II), remains poorly understood. Here, a multifunctional theranostic platform is presented that combines Near‐infrared‐II (NIR‐II) dual‐modal photoacoustic imaging (PAI) with optical coherence tomography angiography (OCTA), enabling comprehensive, multidimensional assessment of tumor hemodynamics, metabolic microstructure, and vascular networks. To enhance therapeutic efficacy and imaging performance, epitaxially Pd@Au‐PEG nanosheets are engineered that synergistically support NIR‐II PTT and multiscale imaging. These nanosheets exhibit strong NIR‐II absorption, high photothermal conversion efficiency, and robust biological stability compared with conventional NIR‐I agents. In vivo experiments demonstrate that this dual‐modal imaging platform provides complementary absorption and scattering‐based contrast, enabling detailed evaluation of tumor growth, hemodynamic progression, margin delineation, vascular remodeling, and microenvironmental changes, as well as real‐time feedback on drug delivery during NIR‐PTT. Collectively, this work establishes a clinically relevant NIR‐II theranostic platform that integrates multiple optical contrast mechanisms to guide targeted NIR‐II PTT with improved precision and efficacy, thereby facilitating individualized treatment planning and response evaluation.