TY - JOUR
T1 - Translational strategies and systems biology insights for blood-brain barrier opening and delivery in brain tumors and Alzheimer's disease
AU - Song, Gefei
AU - Plumlee, Pierce
AU - Ahn, Ju Young
AU - Wong, Stephen TC
AU - Zhao, Hong
N1 - Funding Information:
The authors would like to thank Dr. Rebecca Danforth for proofreading the manuscript. This work was funded by NIH 1R01CA238727 to H.Z. and S.T.W., NIH U01 U01CA253553 to S.T.W., T.T. and W.F. Chao Foundation and John S. Dunn Research Foundation to S.T.W., Houston Methodist Cornerstone Award to H.Z., and the NCI Cancer Systems Biology Consortium (CSBC) Summer Internship Awards to G.S. and P.P.
Publisher Copyright:
© 2023 The Authors
PY - 2023/11
Y1 - 2023/11
N2 - 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.
AB - 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.
KW - Alzheimer's disease
KW - Blood-brain barrier opening
KW - Brain tumors
KW - Clinical studies
KW - CNS drug delivery
KW - Systems biology
KW - Brain
KW - Humans
KW - Systems Biology
KW - Drug Delivery Systems
KW - Blood-Brain Barrier/pathology
KW - Alzheimer Disease/drug therapy
KW - Microbubbles
KW - Brain Neoplasms/drug therapy
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U2 - 10.1016/j.biopha.2023.115450
DO - 10.1016/j.biopha.2023.115450
M3 - Review article
C2 - 37703663
AN - SCOPUS:85171755206
SN - 0753-3322
VL - 167
SP - 115450
JO - Biomedicine and Pharmacotherapy
JF - Biomedicine and Pharmacotherapy
M1 - 115450
ER -