Macrophages-Mediated Delivery of Small Gold Nanorods for Tumor Hypoxia Photoacoustic Imaging and Enhanced Photothermal Therapy

ACS Appl Mater Interfaces. 2019 May 1;11(17):15251-15261. doi: 10.1021/acsami.9b00495. Epub 2019 Apr 17.

Abstract

Macrophage-mediated delivery of drugs or nanoparticles has great potential in cancer treatment because it can avoid interception by the immune system and cross the blood-vessel barriers to reach the hypoxic regions of tumors. However, macrophage-based delivery system still faces some great challenges such as low theranostics agent loading capacity and hypoxic regions tendency in vivo. Herein, small gold nanorods (AuNRs) were used as the model theranostics agent to design a macrophage-mediated delivery system with high loading quantity for tumor hypoxia photoacoustic (PA) imaging and enhanced photothermal therapy (PTT). AuNRs modified with various thiolated poly(ethylene glycol)s (HS-PEG) via ligand exchange were investigated for toxicity and cell uptake by macrophages. The tumor hypoxic regions tendency of macrophage-loaded Anionic-AuNRs (Anionic-AuNRs@RAW) were verified by in vivo PA imaging and tumor sections. In vivo systemic PTT demonstrated enhanced tumor inhibition of anionic-AuNRs@RAW. This macrophage-mediated delivery system with high loading capacity could be used to enhance the effectiveness of cancer treatment.

Keywords: gold nanorods; hypoxia; macrophages; photoacoustic imaging; photothermal therapy.

MeSH terms

  • Animals
  • Biocompatible Materials / chemistry
  • Biocompatible Materials / therapeutic use
  • Biocompatible Materials / toxicity
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Female
  • Gold / chemistry*
  • Humans
  • Hyperthermia, Induced
  • Lasers
  • Macrophages / cytology
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Nanotubes / chemistry*
  • Nanotubes / toxicity
  • Neoplasms / pathology
  • Neoplasms / therapy
  • Photoacoustic Techniques / methods*
  • Phototherapy
  • Polyethylene Glycols / chemistry
  • RAW 264.7 Cells
  • Sulfhydryl Compounds / chemistry
  • Tumor Hypoxia*

Substances

  • Biocompatible Materials
  • Sulfhydryl Compounds
  • Polyethylene Glycols
  • Gold