Zn2+ Doped Ultrasmall Prussian Blue Nanotheranostic Agent for Breast Cancer Photothermal Therapy under MR Imaging Guidance

Abstract

Prussian blue nanoprobes are widely studied and applied in tumor photothermal therapy (PTT) and magnetic resonance imaging (MRI), due to their low toxicity and excellent in vivo performance. However, the sizes of hitherto reported Prussian blue nanoprobes are generally larger than 50 nm, which greatly influence cell phagocytosis, in vivo circulation, and biodistribution. In this work, a novel method of doping zinc ions is used to control the size of Prussian blue nanoprobes. Consequently, the performances of the nanoprobes in PTT and MRI are both significantly improved. The results show that the minimum size of Prussian blue nanoprobes achieved by doping 10% zinc ions (abbreviated as SPBZn(10%)) is 3.8 ± 0.90 nm, and the maximum specific absorption coefficient, photothermal conversion efficiency, and longitudinal relaxation rates are 1.78 L g^-1 cm^-1 , 47.33%, and 18.40 mm^-1 s^-1 , respectively. In addition, the SPBZn(10%) nanoprobes provide excellent PTT efficacy on 4T1 tumor cells (killing rate: 90.3%) and breast cancer model (tumor inhibition rate: 69.4%). Toxicological experiment results show that the SPBZn(n%) nanoprobes exhibit no obvious in vitro cytotoxicity and they can be used safely in mice at doses below 100 mg kg^-1 . Therefore, SPBZn(10%) nanoprobes can potentially be used for effective cancer theranostics.

Keywords: Zn2+ doped ultrasmall Prussian blue; cancer theranostics; magnetic resonance imaging; photothermal therapy.