Development of a tumor-targetable heteropolymetallic lanthanide-complex-based magnetoluminescent probe for dual-modal time-gated luminescence/magnetic resonance imaging of cancer cells in vitro and in vivo†
Probes combining luminescence and magnetic resonance (MR) imaging activities have attracted tremendous attention since they can offer both molecular and anatomical information to effectively improve the accuracy of detection. In this work, a β-diketone ligand (CDHH) was modified by covalent conjugation with an MRI contrast agent (DO3A–Gd) and a tumor-targetable biomacromolecule transferrin (Tf). When Eu3+ ions were added into the mixture of two functionalized β-diketone ligands, they triggered a self-assembly to form a heteropolymetallic lanthanide complex that was conjugated to Tf. The as-prepared bioconjugate, i.e., Tf–Eu–Gd, exhibited intense long-lived luminescence (ϕ = 0.20, τ = 0.34 ms), remarkably high MR relaxivities (r1 = 9.18 mM−1 s−1 and r2 = 12.03 mM−1 s−1), as well as good water solubility, stability, and biocompatibility. Time-gated luminescence (TGL) imaging of live cells using Tf–Eu–Gd as a probe demonstrated that the probe can distinguish Tf-receptor-overexpressed cancerous cells, which enables the probe to be specifically accumulated in these cells. On the basis of magnetoluminescent properties of Tf–Eu–Gd, it was further used as a bimodal probe for both TGL and MR imaging of cancerous cells in tumor-bearing nude mice. The results indicated that Tf–Eu–Gd could significantly increase the T1-weighted MRI contrast value in the tumor region, and the TGL imaging of tumor tissue sections provided clear histological validation of the MRI signals. The research outcomes revealed the feasibility of Tf–Eu–Gd for the tracing and precise detection of cancerous cells, which suggested its potential for serving to the clinical diagnosis, therapy, and medical research of tumor diseases.