Journal
BIOMATERIALS
Volume 32, Issue 26, Pages 6245-6253Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2011.05.004
Keywords
Drug delivery; Protein delivery; Magnetic nanoparticles; Magnetic targeting; MR imaging; Brain tumor targeting
Funding
- NIH [CA114612, NS066945]
- Hartwell Foundation
- World Class University (WCU) of the MEST [R31-2008-000-10103-01]
- NRF of South Korea
- National Basic Research Program of China (973 Program) [2007CB935800]
- University of Michigan
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The delivery of bioactive proteins to tumors is associated with many difficulties that have impeded clinical translation of these promising therapeutics. Herein we present an approach, including (1) use of magnetically-responsive and MRI-visible nanoparticles as drug carriers, (2) topography-optimized intra-arterial magnetic targeting, (3) MRI-guided subject alignment within the magnetic field, and (4) surface modification of the protein drug with membrane-permeable polyethyleneimine (PEI), to prevail over the obstacles in protein delivery. Applying these methodologies, we demonstrated the delivery of a significant quantity of beta-Galactosidase selectively into brain tumors of glioma-bearing rats, while limiting the exposure of normal brain regions. Clinical viability of the technologies utilized, and the ability to deliver proteins at high nanomolar-range tumor concentrations, sufficient to completely eradicate a tumor lesion with existing picomolar-potency protein toxins, renders the prospect of enabling protein-based cancer therapy extremely promising. (C) 2011 Elsevier Ltd. All rights reserved.
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