Lactoferrin-Functionalized CuS Nanoparticles for NIR-II Photoacoutic Imaging-Guided Photothermal Tumor Ablation with ROS Scavenging and Inflammation Alleviating Effects

Photothermal therapy (PTT) in the near-infrared II window (NIR-II, 1000-1700 nm) is favored for noninvasive cancer treatment due to its deep tissue penetration, reduced background interference, and better biosecurity. However, excessive reactive oxygen species (ROS) and inflammatory cytokines during localized hyperthermia limit its therapeutic efficiency. In this work, lactoferrin-functionalized copper sulfide nanoparticles (Lf-CuS NPs) with a hydrodynamic size of 31.2 nm were synthesized via "one-step" biomineralization for NIR-II-guided photothermal therapy. The Lf-CuS NPs exhibited efficient NIR-II light absorption at 1064 nm, high photostability for effective PTT, and desirable ROS scavenging capability for inflammation-resolving therapy. Following a 1064 nm laser irradiation of 1.0 W/cm², 4T1 tumors were efficiently ablated with no recurrence over a 14 day period. Remarkably, Lf-CuS NPs possessed good photoacoustic imaging (PAI) capabilities, enabling real-time monitoring of their accumulation at the target site after intravenous administration. This ensures precise timing for PTT, optimizing therapeutic outcomes while reducing potential damage to the surrounding skin and tissues. Furthermore, the low toxicity of Lf-CuS NPs was confirmed through extensive in vitro and in vivo experiments, highlighting their potential as a promising photothermal agent. In conclusion, this research presents a promising strategy for tumor-targeted therapy and highlights lactoferrin as an inflammation alleviating agent in antitumor application.