Multifunctional low-temperature photothermal nanodrug with in vivo clearance, ROS-Scavenging and anti-inflammatory abilities

Harsh photothermal temperatures, long-term body retention of nanoagents, elevated ROS and inflammation induction all threaten the normal tissues, thus hindering the translation of photothermal therapy (PTT) from bench to clinical practice. To resolve these problems, we have developed a disassembled theranostic nanodrug Qu-(FeP)-P-II based on the quercetin coordination. Herein, quercetin is not only the heat shock protein (Hsp 70) inhibitor but also the skeleton of Qu-(FeP)-P-II, realizing near-infrared light induced low-temperature PTT (45 degrees C) to ablate tumor completely without heat stress to normal tissues. Owing to the ROS scavenging ability of quercetin, Qu-(FeP)-P-II effectively reduces intracellular ROS and in vivo inflammatory factors (TNF-alpha, IL-6, IFN-gamma) levels. Simultaneously, quercetin-Fe coordination is weakened when scavenging ROS, which triggers the Qu-(FeP)-P-II disassembling, resulting in effective clearance of nanoparticles from main organs 168 h post intravenous injection. Additionally, the photoacoustic and magnetic resonance dual-imaging capability of Qu-(FeP)-P-II offers excellent spatial resolution and imaging depth not only for precise tumor diagnosis but also for monitoring the nanodrug disassembling in vivo. Thus, Qu-(FeP)-P-II intrinsically integrates precise diagnosis, excellent low-temperature PTT efficacy, ROS elimination and anti-inflammatory action, dynamic disassembly and renal clearance ability into a single nanodrug, which is very promising for future clinical cancer treatment.