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.

Enhanced and selective delivery of enzyme therapy to 9L-glioma tumor via magnetic targeting of PEG-modified, ß-glucosidase- conjugated iron oxide nanoparticles

“…19 Tissue samples (∼100 mg) were homogenized at 0°C in 50 µL of lysis buffer (Tropix Inc., Bedford, MA, USA) using a pestle tissue grinder. The homogenates were diluted with 950 µL of 100 mmol/L pH 7.0 HEPES buffer containing 100 mmol/L KCL and 1 mmol/L MgSO 4 .…”

“…The amount of conjugated enzyme on MNP was quantified using the bicinchoninic acid protein assay (Thermo Fisher Scientific, Lake Barrington, IL, USA). 19 …”

“…The mouse was then injected with the MNP suspension (12 mg Fe/kg) through the lateral tail vein and kept in the magnetic field for one hour. MRI experiments were carried out with using a protocol described previously with modification 19 using a 30 cm horizontal-bore, 7T Direct Drive small animal imaging system (Varian, Walnut Creek, CA, USA). A thermostated circulating water bath was used to keep the temperature inside the magnet at 37°C throughout the MRI scanning process.…”

Nanotheranostics – a review of recent publications

“…In a recent study carried out by Hu et al 14 the photothermal effect of AuNR was efficiently improved by a surrounding silver shell (AuNR-in-shell). The Chemotherapy X-ray imaging MR imaging [19][20][21][22][23][24][25] [27]…”

“…Moreover, electrostatic interaction has been shown to be the other approach for conjugating delivered substances to magnetic NPs. For instance, Chertok et al 23 have loaded β-galactosidase (β-gal) onto heparin-coated iron-oxide NPs along with complex polyethyleneimine. The resulting nanocarrier exhibited capability in delivering a significant quantity of β-gal selectively into a brain tumor, revealed in a rat glioma model.…”