Renal-clearable hyaluronic acid functionalized NaGdF ₄ nanodots with enhanced tumor accumulation†

Abstract

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 NaGdF ₄ nanodots (named NaGdF ₄ ND@HAs) have been prepared through conjugation of tryptone capped NaGdF ₄ nanodots (NaGdF ₄ ND@tryptone) with hyaluronic acid (HA, a naturally occurring glycosaminoglycan), which can recognize the overexpressed CD44 on cancer cell membranes. The as-prepared NaGdF ₄ 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 NaGdF ₄ 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 NaGdF ₄ 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.

Abstract

Hyaluronic acid functionalized NaGdF ₄ nanodots were synthesized and evaluated as an active tumor-targeting magnetic resonance imaging (MRI) contrast agent.