CXC Chemokine Receptor 4 Antagonist Functionalized Renal Clearable Manganese-Doped Iron Oxide Nanoparticles for Active-Tumor-Targeting Magnetic Resonance Imaging-Guided Bio-Photothermal Therapy

Yu Fu; Xiaodong Li; Hongda Chen; Zhenxin Wang; Wensheng Yang; Huimao Zhang

doi:10.1021/acsabm.9b00475

CXC Chemokine Receptor 4 Antagonist Functionalized Renal Clearable Manganese-Doped Iron Oxide Nanoparticles for Active-Tumor-Targeting Magnetic Resonance Imaging-Guided Bio-Photothermal Therapy

ACS Appl Bio Mater. 2019 Aug 19;2(8):3613-3621. doi: 10.1021/acsabm.9b00475. Epub 2019 Jul 24.

Authors

Yu Fu^{1

2}, Xiaodong Li², Hongda Chen³, Zhenxin Wang³, Wensheng Yang¹, Huimao Zhang²

Affiliations

¹ College of Chemistry, Jilin University, Changchun 130021, P. R. China.
² Department of Radiology, The First Hospital of Jilin University, Changchun 130021, P. R. China.
³ State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, P. R. China.

PMID: 35030748
DOI: 10.1021/acsabm.9b00475

Abstract

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.

Keywords: CXC chemokine receptor 4 antagonist; active-tumor-targeting; bio-photothermal therapy; dual-modal magnetic resonance imaging; manganese-doped iron oxide nanoparticles.