Renal-clearable hyaluronic acid functionalized NaGdF₄ nanodots with enhanced tumor accumulation

Integration of high tumor-targeting capacity, controlling in vivo transport and low normal tissue retention into one engineered nanoparticle is a critical issue for future clinically translatable anti-cancer nanomedicines. Herein, hyaluronic acid functionalized 3.8 nm NaGdF₄ nanodots (named NaGdF₄ ND@HAs) have been prepared through conjugation of tryptone capped NaGdF₄ nanodots (NaGdF₄ ND@tryptone) with hyaluronic acid (HA, a naturally occurring glycosaminoglycan), which can recognize the overexpressed CD44 on cancer cell membranes. The as-prepared NaGdF₄ ND@HAs have good paramagnetic properties (longitudinal relaxivity (r ₁) = 7.57 × 10^-3 M S^-1) and low cytotoxicity. The in vivo experimental results demonstrate that the NaGdF₄ ND@HAs can not only efficiently accumulate in mouse-bearing MDA-MB-231 tumors (ca. 5.3% injection dosage (ID) g^-1 at 2 h post-injection), but also have an excellent renal clearance efficiency (ca. 75% injection dosage (ID) at 24 h post-injection). The as-prepared NaGdF₄ ND@HAs have good paramagnetic properties with enhanced tumor-targeting capacity, which provides a useful strategy for the preparation of renal clearable magnetic resonance imaging (MRI) contrast agents for tumors.