Rutin-encapsulated manganese carbonate nanoparticles for “Liver-dark/tumor-bright” magnetic resonance imaging and inhibition of breast cancer with liver metastases

Abstract Patients with breast cancer liver metastasis (BCLM) have a low survival rate and poor prognosis; thus, early and precise diagnosis and treatment are important. Here, we developed rutin-encapsulated manganese carbonate nanoparticles (RM NPs) for sensitive magnetic resonance imaging (MRI) diagnosis and effective inhibition of BCLM. RM NPs are nanoclusters consisting of manganese carbonate nanocrystals. They have pH-responsive properties and release Mn2+ following their uptake into cells, generating MRI signals. Using a 4T1 mouse liver metastasis mouse model, we demonstrated different uptake rates of RM NPs between normal liver tissue and metastatic tumors. The “liver-dark/tumor-bright” (tumor-to-normal liver contrast ratio reached 219%) phenomenon can be produced using a specific T1WI imaging sequence, which enables precise imaging of submillimeter (less than 1 millimeter) BCLM. In vitro and in vivo experiments confirmed that because of the rutin sugar groups on the surface of RM NPs, they actively target tumor cells with overexpressed glucose transporters (Gluts). After being taken up by tumor cells, RM NPs release rutin, which induces tumor cell apoptosis by upregulating cleaved cysteine protease-3 and thereby inhibiting tumor cell growth and liver metastasis. Overall, RM NPs can serve as an effective and safe theranostic platform for precise MRI and treatment of BCLM.