Ionizing radiation attracts tumor targeting and apoptosis by radiotropic lysyl oxidase traceable nanoparticles

Nanomedicine. 2020 Feb:24:102141. doi: 10.1016/j.nano.2019.102141. Epub 2019 Dec 10.

Abstract

Lysyl oxidase (LOX) is a cell-secreted amine oxidase that crosslinks collagen and elastin in extracellular microenvironment. LOX-traceable nanoparticles (LOXab-NPs) consisting of LOX antibodies (LOXab) and paclitaxel, can accumulate at high concentrations at radiation-treated target sites, as a tumor-targeting drug carrier for chemotherapy. Tumor-targeting and anticancer effects of PLGA based LOXab-NPs in vitro and in vivo were evaluated at radiation-targeted site. In the in vivo A549 lung carcinoma xenograft model, we showed highly specific tumor targeting (above 7.0 times higher) of LOXab-NPs on irradiated tumors. Notably, systemically administered NPs delayed tumor growth, reducing tumor volumes by more than 2 times compared with non-irradiated groups (222% vs. >500%) over 2 weeks. Radiotropic LOXab-NPs can serve as chemotherapeutic vehicles for combined targeted chemo-radiotherapy in clinical oncology.

Keywords: Chemo-radiotherapy; Ionizing radiation; LOX-traceable nanoparticles; Radiotropic; Stimulus inducible; Targeting.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Animals
  • Apoptosis / radiation effects*
  • Blotting, Western
  • Cells, Cultured
  • Female
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Nanoparticles / chemistry*
  • Nanoparticles / therapeutic use*
  • Particle Size
  • Protein-Lysine 6-Oxidase / chemistry
  • Protein-Lysine 6-Oxidase / metabolism*
  • Radiation, Ionizing*
  • Xenograft Model Antitumor Assays

Substances

  • Protein-Lysine 6-Oxidase