A tumor-targetable probe based on europium(iii)/gadolinium(iii) complex-conjugated transferrin for dual-modal time-gated luminescence and magnetic resonance imaging of cancerous cells in vitro and in vivo

Abstract

The synergy of magnetic resonance imaging (MRI) and time-gated luminescence imaging (TGLI) provides a robust platform with extensive spatial resolution (from submicrometer to hundred-micron) and unlimited penetration depth for visual detection of lesion tissues and target biomolecules. In this work, highly stable lanthanide (Eu³⁺ and Gd³⁺) complexes with a terpyridine polyacid ligand, CNSTTA-Ln³⁺, were chosen as signal reporters for TGLI (Ln³⁺ = Eu³⁺) and MRI (Ln³⁺ = Gd³⁺), respectively. After conjugating CNSTTA-Ln³⁺ with a tumor-targetable glycoprotein, transferrin (Tf), the obtained bioconjugate, showed low cytotoxicity and high stability and exhibited strong long-lived luminescence (Tf-CNSTTA-Eu³⁺, ϕ = 10.8%, τ = 1.27 ms), high magnetic resonance relaxivity (Tf-CNSTTA-Gd³⁺, r₁ = 8.70 mM⁻¹ s⁻¹, r₂ = 10.90 mM⁻¹ s⁻¹), and high binding affinity toward Tf receptor-overexpressed cancerous cells. On the basis of these features, a tumor-targetable probe was constructed by simply mixing Tf-CNSTTA-Eu³⁺ and Tf-CNSTTA-Gd³⁺, and successfully used for the bimodal TGLI and MRI of tumor cells in tumor-bearing mice. The bimodal imaging simultaneously provided the anatomical and molecular information of the tumor, which enabled the accuracy for tumor diagnosis to be mutually verified, and revealed the potential of Tf-CNSTTA-Gd³⁺/Eu³⁺ for the monitoring of cancer cells in vivo.