Recent Advances in Functionalized Gold Nanoprobes for Photoacoustic Imaging Analysis of Diseases

Photoacoustic imaging (PAI) integrates the high-contrast merits of optical imaging with the high-spatial-resolution advantages of acoustic imaging, enabling the acquisition of three-dimensional images with deep tissue penetration (up to several centimeters) for in vivo disease detection and diagnosis. Among various photoacoustic nanoagents, gold nanomaterials (GNMs) have been widely explored for the PAI-based imaging analysis and photothermal therapy of diseases, owing to their strong near-infrared (NIR) absorption, which can generate distinct photoacoustic signals in deep tissues. This review focuses on recent advances and achievements in the development of functionalized gold nanoprobes, including Janus gold nanoprobes, gold nanocomposite probes (such as functionally coated GNMs and GNMs-loaded nanocarriers), and gold nanoaggregate probes (e.g., pre-assembly of GNMs and in situ aggregation of GNMs). The multifunctionalization of GNMs can enhance their PAI performance by shifting absorption to the NIR-I and NIR-II regions, while simultaneously imparting additional functionalities such as targeted delivery to disease sites and specific responsiveness to disease biomarkers. These features can render functionalized GNMs-based nanoprobes highly suitable for PAI-based analysis and the precise detection of various pathological conditions, including bacterial infections, tumors, kidney injury, and disorders affecting the ocular, gastrointestinal, cardiovascular, visceral, and lymphatic systems. Finally, this review provides a concise summary of biosafety evaluation and outlines the current challenges and future perspectives in optimizing the GNMs-based PAI methods, highlighting their potential to enhance the rapid and precise diagnosis of diseases in the future.