J. Mater. Sci. Technol. ›› 2021, Vol. 81: 77-87.DOI: 10.1016/j.jmst.2020.11.058

• Research Article • Previous Articles     Next Articles

M2 macrophage-targeted iron oxide nanoparticles for magnetic resonance image-guided magnetic hyperthermia therapy

Wenshen Wanga, Fenfen Lia,*(), Shibo Lia, Yi Hua, Mengran Xub, Yuanyuan Zhanga, Muhammad Imran Khana, Shaozhen Wanga, Min Wub, Weiping Dinga,*(), Bensheng Qiua,*()   

  1. aNational Lab for Physical Sciences at the Microscale and the Centers for Biomedical Engineering, University of Science and Technology of China, Hefei, 230027, China
    bThe First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China
  • Received:2020-07-10 Revised:2020-10-27 Accepted:2020-11-11 Published:2021-01-07 Online:2021-01-07
  • Contact: Fenfen Li,Weiping Ding,Bensheng Qiu
  • About author:bqiu@ustc.edu.cn (B. Qiu).
    wpdings@ustc.edu.cn (W. Ding),
    *National Lab for Physical Sciences at the Microscaleand the Centers for Biomedical Engineering, University of Science and Technologyof China, Hefei, 230027, China.E-mail addresses: lifenfen@ustc.edu.cn (F. Li),

Abstract:

Tumor-associated macrophages (TAMs) play an important role in tumor development and progression. In particular, M2 TAMs can promote tumor growth by facilitating tumor progression and malignant behaviors. Selectively targeted elimination of M2 TAMs to inhibit tumor progression is of great significance for cancer treatment. Iron oxide nanoparticles based magnetic hyperthermia therapy (MHT) is a classical approach to destroy tumor tissue with deep penetration depth. In this study, we developed a typical M2 macrophage-targeted peptide (M2pep) functionalized superparamagnetic iron oxide nanoparticle (SPIO) for magnetic resonance imaging (MRI)-guided MHT in an orthotopic breast cancer mouse model. The obtained multifunctional SPIO-M2pep with a hydrodynamic diameter of 20 nm showed efficient targeting capability, high transverse relaxivity (149 mM-1 s-1) and satisfactory magnetic hyperthermia performance in vitro. In vivo studies demonstrated that the SPIO-M2pep based MRI can monitor the distribution of nanoparticles in tumor and indicate the suitable timing for MHT. The M2 macrophage-targeted MHT significantly reduced the tumor volume and the population of pro-tumoral M2 TAMs in tumor. In addition, the SPIO-M2pep based MHT can remodel the tumor immune microenvironment (TIME). The multifunctional SPIO-M2pep with M2 macrophage-targeting ability, high magnetic hyperthermia efficiency, MR imaging capability and effective role in remodeling the TIME hold great potential to improve clinical cancer therapy outcomes.

Key words: M2 macrophages-targeted peptide, Iron oxide nanoparticles, Magnetic resonance imaging, Magnetic hyperthermia therapy, Tumor immune microenvironment