CXC Chemokine Receptor 4 Antagonist Functionalized Renal Clearable Manganese-Doped Iron Oxide Nanoparticles for...

Herein, multifunctional nanoparticles (MnIO-MCP) have been constructed for active-tumor-targeting T₁-weighted and T₂-weighted (T₁-T₂) dual-modal magnetic resonance imaging (MRI)-guided bio-photothermal therapy (bio-PTT) through bioconjugation of the monocyclic peptides (MCP, the CXC chemokine receptor 4 (CXCR4) antagonist) with manganese-doped iron oxide nanoparticles (MnIO NPs). MnIO-MCP displays both T₁-weighted and T₂-weighted MR contrast abilities (r₁ = 13.1 mM^-1 S^-1; r₂ = 46.6 mM^-1 S^-1, and r₂/r₁ = 3.56), allowing generation of enhanced T₁-T₂ dual-modal MRI. The MnIO-MCP exhibits reasonable photothermal conversion efficiency (28.8% with 200 μg mL^-1 MnIO-MCP in H₂O) under 808 nm NIR laser irradiation, endowing them with the capacity for PTT of a tumor. Moreover, MnIO-MCP affords the strong tumor-targeting and inhibition of cancer cell growth by the interactions of MCP with overexpressed CXCR4 in the tumor. We demonstrate that MnIO-MCP can accumulate in MCF-7 tumors as high as ∼15.9% ID g^-1 at 1 h after intravenous injection into mice with the aid of an external magnetic field (MF), creating the opportunity for complete eradication of the tumor by T₁-T₂ dual-modal MRI-guided bio-PTT.