Gold Nanoclusters Development History in the Sphere of Smart Theranostics: Passive Targeting Mechanisms and Transformation into Microenvironment-Responsive Activation

Due to the numerous advantages of gold nanoparticles, such as ultra-small size, tunable fluorescence, enzyme-like catalysis, and renal clearance capability, the field of nanotheranostics has emerged as a research hotspot. However, the balance between circulatory stability and efficient activation at lesion sites still limits its clinical translation. Following the trajectory of “from passive to active, then to intelligent, and finally to external synergy,” this article systematically reviews the development of AuNCs from 1.0 in a passive targeting state, 2.0 in active targeting, 3.0 in microenvironment-responsive behavior, to 4.0 in multimodal energy field synergy.