Reversibly Modulating the Blood-Brain Barrier by Laser Stimulation of Molecular-Targeted Nanoparticles

Xiaoqing Li, Vamsidhara Vemireddy, Qi Cai, Hejian Xiong, Peiyuan Kang, Xiuying Li, Monica Giannotta, Heather N. Hayenga, Edward Pan, Shashank R. Sirsi, Celine Mateo, David Kleinfeld, Chris Greene, Matthew Campbell, Elisabetta Dejana, Robert Bachoo, Zhenpeng Qin

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

The blood-brain barrier (BBB) is highly selective and acts as the interface between the central nervous system and circulation. While the BBB is critical for maintaining brain homeostasis, it represents a formidable challenge for drug delivery. Here we synthesized gold nanoparticles (AuNPs) for targeting the tight junction specifically and demonstrated that transcranial picosecond laser stimulation of these AuNPs post intravenous injection increases the BBB permeability. The BBB permeability change can be graded by laser intensity, is entirely reversible, and involves increased paracellular diffusion. BBB modulation does not lead to significant disruption in the spontaneous vasomotion or the structure of the neurovascular unit. This strategy allows the entry of immunoglobulins and viral gene therapy vectors, as well as cargo-laden liposomes. We anticipate this nanotechnology to be useful for tissue regions that are accessible to light or fiberoptic application and to open new avenues for drug screening and therapeutic interventions in the central nervous system.

Original languageEnglish (US)
JournalNano Letters
DOIs
StateAccepted/In press - 2021

Keywords

  • blood-brain barrier
  • gold nanoparticle
  • therapeutics delivery
  • tight junction targeting

ASJC Scopus subject areas

  • Bioengineering
  • Chemistry(all)
  • Materials Science(all)
  • Condensed Matter Physics
  • Mechanical Engineering

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