Albumin-Bioinspired Gd:CuS Nanotheranostic Agent for <i>In Vivo</i> Photoacoustic/Magnetic Resonance Imaging-Guided Tumor-Targeted Photothermal Therapy

TLDR

Photothermal therapy is increasingly used for skin cancer due to its noninvasiveness and low systemic side effects. There is an urgent need to develop biocompatible PTT agents that allow accurate imaging, monitoring, and diagnosis. The authors synthesized ultrasmall (≈9 nm) Gd‑integrated CuS nanoparticles using bovine serum albumin as a biotemplate at physiological temperature via a biomimetic strategy. The Gd:CuS@BSA nanoparticles exhibited high photothermal conversion efficiency, excellent photostability, strong NIR absorbance, enabled dual photoacoustic/MRI tumor imaging, achieved effective photothermal ablation, induced a favorable immune response, proved biocompatible, and cleared hepatically, underscoring their practical theranostic potential.

Abstract

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.