FA-NBs-IR780: Novel multifunctional nanobubbles as molecule-targeted ultrasound contrast agents for accurate diagnosis and photothermal therapy of cancer

Cancer Lett. 2019 Jul 28:455:14-25. doi: 10.1016/j.canlet.2019.04.023. Epub 2019 Apr 21.

Abstract

Early accurate diagnosis and targeted therapy for cancer are essential to improve the prognosis of patients. With the emergence of molecular imaging, molecule-targeted ultrasound imaging for the non-invasive and precise detection of cancer has attracted increased attention. The investigation of molecule-targeted ultrasound contrast agents (UCAs) with excellent performance is urgently needed. In this study, we synthetized folic acid and IR-780 on self-made nanobubbles and prepared novel UCAs, named FA-NBs-IR780. The results showed that the conjugates had a uniform size distribution (591 ± 52 nm). In vitro and in vivo experiments demonstrated that FA-NBs-IR780 can target tumour cells via dual molecular targeting, perform enhanced-contrast ultrasound imaging and near-infrared fluorescence (NIRF) imaging for the precise detection of tumours, and induce targeted photothermal therapy in lesions irradiated at 808 nm. Ex vivo experiments further confirmed that FA-NBs-IR780 efficiently induced tumour cell apoptosis and inhibited tumour growth. The newly fabricated FA-NBs-IR780 were observed to be molecule-targeted dual-mode UCAs and may have potential applications in early accurate diagnosis and targeted therapy of cancer in the future.

Keywords: Molecule imaging; Nanobubbles; Near-infrared fluorescence; Photothermal therapy; Ultrasonography.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Breast Neoplasms / diagnostic imaging*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / therapy*
  • Cell Line, Tumor
  • Contrast Media / administration & dosage
  • Contrast Media / chemistry*
  • Contrast Media / pharmacokinetics
  • Female
  • Glioblastoma / diagnostic imaging*
  • Glioblastoma / metabolism
  • Glioblastoma / therapy*
  • Humans
  • Indoles / administration & dosage
  • Indoles / chemistry*
  • Indoles / pharmacokinetics
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Microbubbles
  • Nanocapsules / administration & dosage
  • Nanocapsules / chemistry
  • Phototherapy / methods*
  • Random Allocation
  • Tissue Distribution
  • Ultrasonography / methods
  • Xenograft Model Antitumor Assays

Substances

  • 2-(2-(2-chloro-3-((1,3-dihydro-3,3-dimethyl-1-propyl-2H-indol-2-ylidene)ethylidene)-1-cyclohexen-1-yl)ethenyl)-3,3-dimethyl-1-propylindolium
  • Contrast Media
  • Indoles
  • Nanocapsules