Photothermal therapy (PTT) is attracting increasing interest and becoming more widely used for skin cancer therapy in the clinic, as a result of its noninvasiveness and low systemic adverse effects. However, there is an urgent need to develop biocompatible PTT agents, which enable accurate imaging, monitoring, and diagnosis. Herein, a biocompatible Gd-integrated CuS nanotheranostic agent (Gd:CuS@BSA) was synthesized via a facile and environmentally friendly biomimetic strategy, using bovine serum albumin (BSA) as a biotemplate at physiological temperature. The as-prepared Gd:CuS@BSA nanoparticles (NPs) with ultrasmall sizes (ca. 9 nm) exhibited high photothermal conversion efficiency and good photostability under near-infrared (NIR) laser irradiation. With doped Gd species and strong tunable NIR absorbance, Gd:CuS@BSA NPs demonstrate prominent tumor-contrasted imaging performance both on the photoacoustic and magnetic resonance imaging modalities. The subsequent Gd:CuS@BSA-mediated PTT result shows high therapy efficacy as a result of their potent NIR absorption and high photothermal conversion efficiency. The immune response triggered by Gd:CuS@BSA-mediated PTT is preliminarily explored. In addition, toxicity studies in vitro and in vivo verify that Gd:CuS@BSA NPs qualify as biocompatible agents. A biodistribution study demonstrated that the NPs can undergo hepatic clearance from the body. This study highlights the practicality and versatility of albumin-mediated biomimetic mineralization of a nanotheranostic agent and also suggests that bioinspired Gd:CuS@BSA NPs possess promising imaging guidance and effective tumor ablation properties, with high spatial resolution and deep tissue penetration.
