Polyethyleneimine-modified iron oxide nanoparticles for brain tumor drug delivery using magnetic targeting and intra-carotid administration

Abstract

This study aimed to examine the applicability of polyethyleneimine (PEI)-modified magnetic nanoparticles (GPEI) as a potential vascular drug/gene carrier to brain tumors. In vitro, GPEI exhibited high cell association and low cell toxicity -properties which are highly desirable for intracellular drug/gene delivery. In addition, a high saturation magnetization of 93 emu/g Fe was expected to facilitate magnetic targeting of GPEI to brain tumor lesions. However, following intravenous administration, GPEI could not be magnetically accumulated in tumors of rats harboring orthotopic 9L-gliosarcomas due to its poor pharmacokinetic properties, reflected by a negligibly low plasma AUC of 12 ± 3 μg Fe/ml*min. To improve "passive" GPEI presentation to brain tumor vasculature for subsequent "active" magnetic capture, we examined the intra-carotid route as an alternative for nanoparticle administration. Intra-carotid administration in conjunction with magnetic targeting resulted in 30-fold (p = 0.002) increase in tumor entrapment of GPEI compared to that seen with intravenous administration. In addition, magnetic accumulation of cationic GPEI (ζ-potential = + 37.2 mV) in tumor lesions was 5.2-fold higher (p = 0.004) than that achieved with slightly anionic G100 (ζ-potential = −12 mV) following intra-carotid administration, while no significant accumulation difference was detected between the two types of nanoparticles in the contra-lateral brain (p = 0.187). These promising results warrant further investigation of GPEI as a potential cellpermeable, magnetically-responsive platform for brain tumor delivery of drugs and genes.

Maghemite Functionalization for Antitumor Drug Vehiculization

“…As this study demonstrates, when drug-loaded nanospheres were administrated in the carotid artery with combination of magnetic targeting, an increase of 30 times in tumor capture of nanospheres was observed as compared to intravenous administration (Chertok et al, 2010). In another interesting investigation functionalized dendrimers which may in effect pass over the BBB and concentrate within malignant glioma cells have been prepared.…”

Characterization of cellular uptake and toxicity of aminosilane-coated iron oxide nanoparticles with different charges in central nervous system-relevant cell culture models

“…The bEnd.3 cells (passage number [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] were cultured in Dulbecco's Modified Eagle Medium (DMEM) (Hyclone, Logan, UT) supplemented with 10% heat-inactivated fetal bovine serum (FBS; Hyclone), 50 U/ mL penicillin and streptomycin (MP Biomedicals, Solon, OH, USA) at 37°C and 5% CO 2 . Cells were expanded in T-75 tissue culture flasks and seeded at 2 × 10 4 cells per cm 2 on six-or twelve-well plates for uptake and cytotoxicity studies, respectively.…”

Magnetic nanoparticle drug delivery systems for targeting tumor

“…Figure 7 shows the MRI head scans of 9L glioma bearing rats. This figure clearly indicates the presence of iron oxide nanoparticles in the tumor lesion (Chertok et al 2010). Ito et al were the first to target esophageal cancer in rabbits by oral administration under the influence of a magnetic field in 1990 (Ito et al 1990).…”

“…The results in vitro showed high cell association and low cellular toxicity. However, initial investigation conducted in vivo in the absence of the magnetic field did not successfully accumulate magnetic nanoparticles onto tumors of rats harboring orthotopic 9L-gliosarcomas, due to poor pharmacokinetic properties (Chertok et al 2010). However, intra-carotid administration in conjunction with magnetic targeting resulted in 30-fold (p = 0.002) increase in tumor entrapment of GPEI compared to that seen with intravenous administration (Fig.…”