title: Magnetically-enabled and MR-monitored selective brain tumor protein delivery in rats via magnetic nanocarriers.
abstract: 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 β-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.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Beata
authors.initials: B
authors.lastname: Chertok
authors.forename: Allan E
authors.initials: AE
authors.lastname: David
authors.forename: Victor C
authors.initials: VC
authors.lastname: Yang
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D001932:Brain Neoplasms / Q000188:drug therapy*; D004337:Drug Carriers / Q000737:chemistry*; D008279:Magnetic Resonance Imaging; D008297:Male; D053758:Nanoparticles / Q000737:chemistry*; D011094:Polyethyleneimine / Q000737:chemistry*; D051381:Rats; D011916:Rats, Inbred F344; D001616:beta-Galactosidase / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*
chemical_list: D004337:Drug Carriers; D011094:Polyethyleneimine; D001616:beta-Galactosidase