High-Performance Worm-like Mn-Zn Ferrite Theranostic Nanoagents and the Application on Tumor Theranostics

ACS Appl Mater Interfaces. 2019 Aug 21;11(33):29536-29548. doi: 10.1021/acsami.9b08948. Epub 2019 Aug 6.

Abstract

Previous reports from our team revealed the significant potential advantage of Mn-Zn ferrite nanoparticles (NPs) in magnetic resonance imaging (MRI), whereas anisotropic NPs reportedly increased the blood circulation time of nanocarriers. Thus, anisotropic Mn-Zn ferrite displayed a huge potential in cancer synchronous diagnosis and treatment, that is, enhanced MRI observation was performed simultaneously when drug-targeted delivery therapy was applied to the tumor. Here, we developed three shaped Mn-Zn ferrite (Mn0.63Zn0.37Fe2O4) MNPs used as cancer theranostic nanoagents and compared the effect of the three shaped MNPs on cancer theranostics. Compared to the monodisperse sphere MNPs (S-MNPs-PPR) and clustering MNPs (C-MNPs-PPR), worm-like Mn-Zn ferrite MNPs (W-MNPs-PPR) achieved better results in T2-weighted MRI and achieved more sustained drug release than S-MNPs-PPR and more complete drug release than C-MNPs-PPR in vitro. Additionally, polyethylene glycol (PEG) coating and RGD modification encouraged the three shaped MNPs to evade the recruitment of macrophages more easily and to target the integrin-enriched endothelial cells instead. Meanwhile, W-MNPs-PPR coupled with Paclitaxel (PTX) exhibited more delivery of PTX in the integrin-enriched cells than the other two shaped MNPs, and the content of PTX was far more than that of the wild-type Taxol control group. What is more, in vivo results demonstrated that PTX-coated W-MNPs-PPR not only gained good dual-mode imaging in the tumor (MRI and fluorescence images) but also achieved longer blood circulation time and more PTX-targeted delivery to the tumor, as well as more efficiency in tumor cell killing, which make the simultaneous diagnosis and treatment of tumors to be conducted. Therefore, our works further revealed the importance of the NP shape on its functionality and ultimately provided an alternative and efficient worm-like theranostic nanoagent for tumor theranostics.

Keywords: Mn−Zn ferrite; nanocarriers; nanotechnology for diagnosis and treatment; shape effects; tumor theranostics.

MeSH terms

  • Animals
  • Breast Neoplasms / drug therapy
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Female
  • Ferric Compounds / chemistry*
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • In Situ Nick-End Labeling
  • Magnetic Resonance Spectroscopy
  • Manganese / chemistry*
  • Mice
  • Mice, Inbred BALB C
  • Nanoparticles / chemistry*
  • Paclitaxel / chemistry
  • Paclitaxel / pharmacology
  • Paclitaxel / therapeutic use
  • Polyethylene Glycols / chemistry
  • RAW 264.7 Cells
  • Spectroscopy, Near-Infrared
  • Theranostic Nanomedicine / methods*
  • Zinc / chemistry*

Substances

  • Ferric Compounds
  • ferrite
  • Polyethylene Glycols
  • Manganese
  • Zinc
  • Paclitaxel