Journal
MOLECULAR PHARMACEUTICS
Volume 10, Issue 10, Pages 3892-3902Publisher
AMER CHEMICAL SOC
DOI: 10.1021/mp400360q
Keywords
magnetic targeting; iron oxide nanoparticles; heparin; 9L-glioma; magnetic resonance imaging
Funding
- National Institutes of Health (NIH) [CA114612, NS066945]
- Hartwell Foundation Biomedical Research Award
- World Class University (WCU) project of South Korea [R31-2008-000-10103-01]
- National Basic Research Program of China (973 Program) [2013CB932502]
Ask authors/readers for more resources
Starch-coated, PEGylated, and heparin-functionalized iron oxide magnetic nanoparticles (DNPH) were successfully synthesized and characterized in detail. The PEGylation (20 kDa) process resulted in an average coating of 430 PEG molecules per nanoparticle. After that, heparin conjugation was carried out to attain the final DNPH platform with 35.4 mu g of heparin/mg of Fe. Commercially acquired heparin-coated magnetic nanoparticles were also PEGylated (HP) and characterized for comparison. Protamine was selected as a model protein to demonstrate the strong binding affinity and high loading content of DNPH for therapeutically relevant cationic proteins. DNPH showed a maximum loading of 22.9 mu g of protamine/mg of Fe. In the pharmacokinetic study, DNPH displayed a long-circulating half-life of 9.37 h, 37.5-fold longer than that (0.15 h) of HP. This improved plasma stability enabled extended exposure of DNPH to the tumor lesions, as was visually confirmed in a flank 9L-glioma mouse model using magnetic resonance imaging (MM). Quantitative analysis of the Fe content in excised tumor lesions further demonstrated the superior tumor targeting ability of DNPH, with up to 31.36 mu g of Fe/g of tissue (13.07% injected dose (I.D.)/g of tissue) and 7.5-fold improvement over that (4.27 mu g of Fe/g of tissue; 1.78% I.D./g of tissue) of HP. Overall, this study shed light on the potential of DNPH to be used as a protein drug delivery platform.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available