ArticleProceedings of the National Academy of Sciences of the United States of America2018
Mechanisms of enhanced drug delivery in brain metastases with focused ultrasound-induced blood-tumor barrier disruption.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 139 papers.
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Who cites it
139 citing papers in PubMed, 230 citations in OpenAlex.
- Evaluation of CNS xenograft brain tumour response to MRI-guided focused ultrasound in combination with radiation therapy.British journal of cancer · 2026Article
- Antibody-drug conjugates in breast cancer brain and leptomeningeal metastases: mechanistic insights and therapeutic progress.Cancer metastasis reviews · 2026Review
- A multiphysics computational model of focused ultrasound-enhanced drug delivery using temperature-sensitive liposomes.Biomechanics and modeling in mechanobiology · 2026Article
- Focused ultrasound for brain metastases.Neuro-oncology advances · 2026Review
- Nanoscale delivery systems for hepatocellular carcinoma: Functionalization, delivery strategies, and clinical challenges.Materials today. Bio · 2026Review
- Fully Humanized Bispecific T Cell Engager Shows Potent Activity in Central Nervous System and Peripheral Tumors.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Data-Driven Feedback Identifies Focused Ultrasound Exposure Regimens for Improved Nanotheranostic Targeting of the Brain.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Bridging the blood-brain barrier: strategies to improve delivery of biologics to tumors in the brain.Fluids and barriers of the CNS · 2026Review
- Mechanisms, Imaging Phenotypes, and Therapeutic Advances of Neovascularization in Brain Metastases.Biomedicines · 2026Review
- Combined Docetaxel-Loaded Perfluorocarbon Nanodroplets with Ultrasound-Mediated Blood-Brain Barrier Disruption for Effective Glioblastoma Treatment in Mice Model.International journal of nanomedicine · 2026Article
- Synergy of radiotherapy, focused ultrasound, and immunotherapy in the treatment of brain metastases.Journal of neuro-oncology · 2025Review
- Abnormal vasculature reduces overlap between drugs and oxygen in a tumour computational model: Implications for therapeutic efficacy.PLoS computational biology · 2025Article
- Acoustic emissions dose and spatial control of blood-brain barrier opening with focused ultrasound.Device · 2025Article
- Sonodynamic Therapy With Orally Absorbable Nanomedicine for Brain Tumor.Brain tumor research and treatment · 2025Review
- Manipulating anthracyclines for deeper tissue penetration and implications for glycolytic tissues.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Multiscale mathematical model-informed reinforcement learning optimizes combination treatment scheduling in glioblastoma evolution.Science advances · 2025Article
- Blood-brain barrier alterations as an initiator of brain metastasis from lung cancer: a new take on an old story.Cancer gene therapy · 2025Review
- Old Tools in a New Era: The Continued Relevance of Chemotherapy in Pediatric Neuro-Oncology.Current oncology (Toronto, Ont.) · 2025Review
- Glioblastoma at the crossroads: current understanding and future therapeutic horizons.Signal transduction and targeted therapy · 2025Review
- Delivery of LOXL1-AS1-siRNAs using targeting peptide-engineered extracellular vesicles with focused ultrasound to suppress medulloblastoma metastasis.Journal of nanobiotechnology · 2025Article
79 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
Blood-brain/blood-tumor barriers (BBB and BTB) and interstitial transport may constitute major obstacles to the transport of therapeutics in brain tumors. In this study, we examined the impact of focused ultrasound (FUS) in combination with microbubbles on the transport of two relevant chemotherapy-based anticancer agents in breast cancer brain metastases at cellular resolution: doxorubicin, a nontargeted chemotherapeutic, and ado-trastuzumab emtansine (T-DM1), an antibody-drug conjugate. Using an orthotopic xenograft model of HER2-positive breast cancer brain metastasis and quantitative microscopy, we demonstrate significant increases in the extravasation of both agents (sevenfold and twofold for doxorubicin and T-DM1, respectively), and we provide evidence of increased drug penetration (>100 vs. <20 µm and 42 ± 7 vs. 12 ± 4 µm for doxorubicin and T-DM1, respectively) after the application of FUS compared with control (non-FUS). Integration of experimental data with physiologically based pharmacokinetic (PBPK) modeling of drug transport reveals that FUS in combination with microbubbles alleviates vascular barriers and enhances interstitial convective transport via an increase in hydraulic conductivity. Experimental data demonstrate that FUS in combination with microbubbles enhances significantly the endothelial cell uptake of the small chemotherapeutic agent. Quantification with PBPK modeling reveals an increase in transmembrane transport by more than two orders of magnitude. PBPK modeling indicates a selective increase in transvascular transport of doxorubicin through small vessel wall pores with a narrow range of sizes (diameter, 10-50 nm). Our work provides a quantitative framework for the optimization of FUS-drug combinations to maximize intratumoral drug delivery and facilitate the development of strategies to treat brain metastases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.