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 作者： Juliane Nguyen¹, Shaolie S. Hossain²³, Johann R. N. Cooke⁴, Jason A. Ellis⁵, Michael B. Deci¹, Charles W. Emala⁴, Jeffrey N. Bruce⁵, Irving J. Bigio⁶⁷, Robert M. Straubinger¹⁸, Shailendra Jo shi⁴⁹

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

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

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

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

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

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

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

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

⁹.Department of Anesthesiology, College of Physicians and Surgeons, Columbia University, New York, USA

 

摘要：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.