Sub 5 nm Gd3+–Hemoporfin Framework Nanodots for Augmented Sonodynamic Theranostics and Fast Renal Clearance

Abstract Metal–organic nanomaterials have emerged as promising therapeutic agents to produce reactive oxygen species (ROS) under ultrasound (US) or light irradiation for tumor treatments. However, their relatively large sizes (ranging from tens to hundreds of nanometers) usually lead to low ROS utilization and body metabolism, thus enlarging their long‐term toxicity and low therapeutic effect. To solve these shortcomings, herein the ultrasmall Gd 3+ –hemoporfin framework nanodots (GdHF‐NDs， ≈5 nm) is reported as efficient nano‐sonosensitizers. Compared with GdHF aggregation (GdHF‐A, ≈400 nm), the ultrasmall GdHF‐NDs generate 2.3‐fold toxic ROS amount under similar conditions, due to shorter diffusion path and larger relative specific surface area. When the GdHF‐NDs dispersion is introvenously injected into tumor‐bearing mouse, they are accumulated within tumors to provide high magnetic resonance imaging (MRI) contrast. Under US irradiation, the GdHF‐NDs achieve a better sonodynamic therapeutic efficacy for tumors, compared with that from GdHF‐A. More importantly, owing to ultrasmall size, most of GdHF‐NDs can be rapidly cleared through the renal pathway. Therefore, GdHF‐NDs can be used as a biosafety and high‐performance sonodynamic agent for cancer theranostics.