Translational strategies and systems biology insights for blood-brain barrier opening and delivery in brain tumors and Alzheimer's disease

Gefei Song, Pierce Plumlee, Ju Young Ahn, Stephen TC Wong, Hong Zhao

Research output: Contribution to journalReview articlepeer-review

3 Scopus citations

Abstract

The blood-brain barrier (BBB) plays a critical role in determining the effectiveness of systemic treatments for brain diseases. Over the years, several innovative approaches in BBB opening and drug delivery have been developed and progressed into clinical testing phases, including focused ultrasound (FUS) with circulating microbubbles, mannitol-facilitated delivery of anti-neoplastic drugs, receptor-mediated transcytosis (RMT) by antibody-drug conjugates (ADCs), and viral vectors for gene therapy. We provided a comprehensive review of the most recent clinical applications of these approaches in managing brain tumors and Alzheimer's disease (AD), two major devastating brain diseases. Moreover, the spatial-temporal molecular heterogeneity of the BBB under disease states emphasized the importance of utilizing emerging spatial systems biology approaches to unravel novel targets for intervention within BBB and tailor strategies for enhancing drug delivery to the brain. Search strategy and selection criteria: Data for this Review were identified by searches of clinicaltrials.gov, MEDLINE, Current Contents, PubMed, and references from relevant articles using the search terms “blood-brain barrier”, “CNS drug delivery”, “BBB modulation”, “clinical trials”, “systems biology”, “primary or metastatic brain tumors”, “Alzheimer's disease”. Abstracts and reports from meetings were included only when they related directly to previously published work. Only articles published in English between 1980 and 2023 were included.

Original languageEnglish (US)
Article number115450
Pages (from-to)115450
JournalBiomedicine and Pharmacotherapy
Volume167
DOIs
StatePublished - Nov 2023

Keywords

  • Alzheimer's disease
  • Blood-brain barrier opening
  • Brain tumors
  • Clinical studies
  • CNS drug delivery
  • Systems biology
  • Brain
  • Humans
  • Systems Biology
  • Drug Delivery Systems
  • Blood-Brain Barrier/pathology
  • Alzheimer Disease/drug therapy
  • Microbubbles
  • Brain Neoplasms/drug therapy

ASJC Scopus subject areas

  • Pharmacology

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