Cell-cargo mediated ZrN nanoparticle for the synergetic phototherapy on both of mice and rabbits

Eur J Pharm Biopharm. 2020 Apr:149:163-169. doi: 10.1016/j.ejpb.2020.02.006. Epub 2020 Feb 19.

Abstract

Realization of phototherapy on the big animal modal with orthotopic tumor is of considerable significance in view of its great clinical relevance to the human deep tumor treatment. Herein, near infrared (NIR)-active ZrN nanoparticles were chosen for both of photothermal and photodynamic purposes to achieve the synergetic phototherapy on mice with subcutaneous tumor and even rabbits bearing with orthotopic tumor. Broad and strong photoabsorption, photosensitive ROS generation and photothermal effect of ZrN nanoparticles together made it to be ideal candidate for the effective tumor photoablation. Meanwhile, cell-cargo of macrophage enables targeted delivery of ZrN nanoparticles without influence on its photophysical properties. Resultantly, macrophage loaded ZrN could efficiently mediate synergetic phototherapeutic outcome as proved by complete removal of solid tumor from mice and rabbits. In this work, we also introduced B-mode ultrasonography and contrast-enhanced ultrasound technique for monitoring the evolution process of deep orthotopic tumor on rabbits post-treatment and confirmed the pathological changes of vascular degeneration and liquefaction necrosis post phototherapy.

Keywords: Macrophage; Orthotopic tumor; Photodynamic therapy; Photothermal therapy; ZrN nanoparticles.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Female
  • Humans
  • Macrophages / metabolism
  • Metal Nanoparticles*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasms / therapy*
  • Photochemotherapy / methods
  • Phototherapy / methods*
  • Rabbits
  • Reactive Oxygen Species / metabolism
  • Ultrasonography / methods
  • Zirconium / chemistry*

Substances

  • Reactive Oxygen Species
  • Zirconium