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Flow arrest intra-arterial delivery of small TAT-decorated and neutral micelles to gliomas

  • Laboratory Investigation
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Abstract

The cell-penetrating trans-activator of transcription (TAT) is a cationic peptide derived from human immunodeficiency virus-1. It has been used to facilitate macromolecule delivery to various cell types. This cationic peptide is capable of crossing the blood–brain barrier and therefore might be useful for enhancing the delivery of drugs that target brain tumors. Here we test the efficiency with which relatively small (20 nm) micelles can be delivered by an intra-arterial route specifically to gliomas. Utilizing the well-established method of flow-arrest intra-arterial injection we compared the degree of brain tumor deposition of cationic TAT-decorated micelles versus neutral micelles. Our in vivo and post-mortem analyses confirm glioma-specific deposition of both TAT-decorated and neutral micelles. Increased tumor deposition conferred by the positive charge on the TAT-decorated micelles was modest. Computational modeling suggested a decreased relevance of particle charge at the small sizes tested but not for larger particles. We conclude that continued optimization of micelles may represent a viable strategy for targeting brain tumors after intra-arterial injection. Particle size and charge are important to consider during the directed development of nanoparticles for intra-arterial delivery to brain tumors.

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Funding

National Cancer Institute at the National Institutes of Health RO1-CA-138643.

Author information

Authors and Affiliations

  1. Department of Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA

    Juliane Nguyen, Michael B. Deci & Robert M. Straubinger

  2. Institute for Computational Engineering and Sciences, University of Texas at Austin, Austin, TX, USA

    Shaolie S. Hossain

  3. Department of Molecular Cardiology, Texas Heart Institute, Houston, TX, USA

    Shaolie S. Hossain

  4. Department of Anesthesiology, Columbia University Medical Center, New York, NY, USA

    Johann R. N. Cooke, Charles W. Emala & Shailendra Joshi

  5. Department of Neurological Surgery, Columbia University Medical Center, New York, NY, USA

    Jason A. Ellis & Jeffrey N. Bruce

  6. Department of Electrical Engineering, Boston University, Boston, MA, USA

    Irving J. Bigio

  7. Department of Biomedical Engineering, Boston University, Boston, MA, USA

    Irving J. Bigio

  8. Department of Pharmacology & Therapeutics, Roswell Park Cancer Institute, Buffalo, NY, USA

    Robert M. Straubinger

  9. Department of Anesthesiology, College of Physicians and Surgeons, Columbia University, 630 West 168th Street, P&S Box 46, New York, NY, 10032, USA

    Shailendra Joshi

Authors
  1. Juliane Nguyen
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  2. Shaolie S. Hossain
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  3. Johann R. N. Cooke
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  4. Jason A. Ellis
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  10. Shailendra Joshi
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Corresponding author

Correspondence to Shailendra Joshi.

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The authors declare that they have no conflict of interest.

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed were in accordance with the ethical standards of Columbia University.

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Nguyen, J., Hossain, S.S., Cooke, J.R.N. et al. Flow arrest intra-arterial delivery of small TAT-decorated and neutral micelles to gliomas. J Neurooncol 133, 77–85 (2017). https://doi.org/10.1007/s11060-017-2429-5

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  • DOI: https://doi.org/10.1007/s11060-017-2429-5

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