Development and MPI tracking of novel hypoxia-targeted theranostic exosomes

Biomaterials. 2018 Sep;177:139-148. doi: 10.1016/j.biomaterials.2018.05.048. Epub 2018 May 29.

Abstract

Treating the hypoxic region of the tumor remains a significant challenge. The goals of this study are to develop an exosome platform that can target regions of tumor hypoxia and that can be monitored in vivo using magnetic particle imaging (MPI). Four types of exosomes (generated under hypoxic or normoxic conditions, and with or without exposure to X-ray radiation) were isolated from MDA-MB-231 human breast cancer cells. Exosomes were labeled by DiO, a fluorescent lipophilic tracer, to quantify their uptake by hypoxic cancer cells. Subsequently, the exosomes were modified to carry SPIO (superparamagnetic iron oxide) nanoparticles and Olaparib (PARP inhibitor). FACS and fluorescence microscopy showed that hypoxic cells preferentially take up exosomes released by hypoxic cells, compared with other exosome formulations. In addition, the distribution of SPIO-labeled exosomes was successively imaged in vivo using MPI. Finally, the therapeutic efficacy of Olaparib-loaded exosomes was demonstrated by increased apoptosis and slower tumor growth in vivo. Our novel theranostic platform could be used as an effective strategy to monitor exosomes in vivo and deliver therapeutics to hypoxic tumors.

Keywords: Cancer; Drug delivery; Exosomes; Hypoxia; Magnetic particle imaging (MPI).

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / therapeutic use
  • Apoptosis / drug effects
  • Breast Neoplasms / diagnostic imaging*
  • Breast Neoplasms / therapy*
  • Cell Line, Tumor
  • Drug Carriers / chemistry*
  • Drug Delivery Systems
  • Exosomes / chemistry*
  • Female
  • Flow Cytometry / methods
  • Fluorescent Dyes / chemistry
  • Humans
  • Magnetics / methods
  • Magnetite Nanoparticles / chemistry
  • Mice, Nude
  • Microscopy, Fluorescence / methods
  • Phthalazines / administration & dosage*
  • Phthalazines / therapeutic use
  • Piperazines / administration & dosage*
  • Piperazines / therapeutic use
  • Theranostic Nanomedicine / methods*
  • Tumor Hypoxia / drug effects

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Fluorescent Dyes
  • Magnetite Nanoparticles
  • Phthalazines
  • Piperazines
  • olaparib