A Biomimetic Au-Polyphenol-CuS Photothermal Agent with Acid-Triggered Disassembly for Enhanced Photothermal Conversion

Nanomaterials offer enhanced stability and functionality for photothermal agents; however, their efficacy is often limited by suboptimal cellular internalization and photothermal conversion efficiency. To address these challenges, we designed a multicomponent inorganic–organic hybrid photothermal agent that integrates a virus-mimicking morphology and stimuli-responsive components. Gold nanostars (GNS) were functionalized with a pH-responsive epigallocatechin gallate (EGCG) polyphenol network, followed by in situ growth of CuS, yielding star-shaped GEC nanoassemblies with a rough surface. This biomimetic design leverages (i) the plasmonic photothermal properties of the GNS core, (ii) the acid-triggered disassembly of the EGCG network (mimicking viral protein shells), and (iii) the in situ synthesized CuS layer exhibiting a virus-mimetic rough surface and targeting capability, which enhances near-infrared light absorption and promotes endocytosis by the target cells. The synergistic integration of GNS and CuS significantly enhanced the photothermal conversion efficiency. Under tumor acidic conditions, the EGCG network disintegrated, leading to the shedding of the CuS shell and a reduction in overall size, which facilitated deep tissue penetration. Structural characterization confirmed the hierarchical architecture and pH-responsive size transition. Compared to unmodified GNS, the cellular uptake of GEC by 4T1 cells was approximately 4.5-fold higher, attributable to its virus-like rough surface, acid-responsive disintegration, and targeting ability. This work demonstrates a rational biomimetic strategy for engineering stimuli-responsive inorganic–organic hybrids with optimized photothermal performance through biomimetic component engineering.