An Enzyme-Like Activity Nanoprobe Based on Fe(III)-Rutin Hydrate Biomineral for MR Imaging and Therapy of Triple Negative Breast Cancer

The diagnosis and treatment of triple-negative breast cancer (TNBC) is still a grand challenge, because there is rare target to be manipulated. Here, an integrated functional nanoprobe is developed for precise diagnosis and treatment of TNBC, based on biominerals of Fe3+ and rutin hydrate (RH), a type of natural flavonoid. Owing to the adjacent phenol hydroxyl groups of RH, Fe3+ can biomineralize with RH to form nanoprobe colloidally stabilized by coating of poly(vinyl pyrrolidone) (PVP). In the nanoprobe, the flavonol central scaffold as well as the glucoside and rhamnose groups can interact specifically with glucose transporters. Once taken by tumor cells, protonation of phenol hydroxyl groups in the weakly acidic lysosomes would lead to release of Fe3+, inducing tumor cell death through a ferroptosis/apoptosis hybrid pathway. Meanwhile, the remaining Fe(III)-RH complex can serve as a photothermal therapy (PTT) agent upon near infrared laser irradiation. Additionally, the Fe(III)-RH/PVP nanoprobe is expected to be eliminated through renal clearance if the nanoprobe formed in the presence of PVP have an appropriately small hydrated diameter. The present work provides a novel design integrated with magnetic resonance imaging capacity, therapeutic functions of Fe3+, and the PTT effect of nanoprobe for TNBC with anticipated biosafety.