An Advanced In Situ Magnetic Resonance Imaging and Ultrasonic Theranostics Nanocomposite Platform: Crossing the Blood-Brain Barrier and Improving the Suppression of Glioblastoma Using Iron-Platinum Nanoparticles in Nanobubbles

ACS Appl Mater Interfaces. 2021 Jun 16;13(23):26759-26769. doi: 10.1021/acsami.1c04990. Epub 2021 Jun 2.

Abstract

Glioblastoma (GBM) is one of the deadliest and most invasive brain cancers/gliomas, and there is currently no established way to treat this disease. The treatment of GBM typically involves intracranial surgery followed by chemotherapy. However, the blood-brain barrier (BBB) impedes the delivery of the chemotherapeutic drug, making the treatment challenging. In this study, we embedded a chemotherapeutic drug and other nanomaterials into a nanobubble (NB), utilized active tracking and other guidance mechanisms to guide the nanocomposite to the tumor site, and then used high-intensity focused ultrasound oscillation to burst the nanobubbles, generating a transient cavitation impact on the BBB and allowing the drug to bypass it and reach the brain. FePt enhances the resolution of T2-weighted magnetic resonance imaging images and has magnetic properties that help guide the nanocomposite to the tumor location. FePt nanoparticles were loaded into the hydrophobic core of the NBs along with doxorubicin to form a bubble-based drug delivery system (Dox-FePt@NB). The surface of the NBs is modified with a targeting ligand, transferrin (Dox-FePt@NB-Tf), giving the nanocomposite active tracking abilities. The Dox-FePt@NB-Tf developed in the present study represents a potential breakthrough in GBM treatment through improved drug delivery and biological imaging.

Keywords: FePt nanoparticles; blood−brain barrier; glioblastoma treatment; magnetic resonance imaging; nanobubbles.

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / pharmacology
  • Apoptosis
  • Blood-Brain Barrier / metabolism*
  • Brain Neoplasms / diagnostic imaging
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / pathology
  • Cell Proliferation
  • Doxorubicin / pharmacology*
  • Drug Delivery Systems*
  • Glioblastoma / diagnostic imaging
  • Glioblastoma / drug therapy*
  • Glioblastoma / pathology
  • Humans
  • Iron / chemistry*
  • Magnetic Resonance Imaging
  • Metal Nanoparticles / administration & dosage*
  • Metal Nanoparticles / chemistry
  • Mice
  • Nanocomposites / chemistry
  • Platinum / chemistry*
  • Precision Medicine
  • Tumor Cells, Cultured
  • Ultrasonics / methods
  • Xenograft Model Antitumor Assays

Substances

  • Antibiotics, Antineoplastic
  • Platinum
  • Doxorubicin
  • Iron