Superparamagnetic Iron Oxide Nanoparticles Encapsulated in Polyethylene Glycol Modified Polymeric Micelles for MRI-Guided Drug and Gene Delivery
Date Issued
2010
Date
2010
Author(s)
Kuo, Hsuan-Ting
Abstract
Over the past several years, cancer has become one of the most devastating diseases worldwide. Nowadays, cancer treatment is much dependent on surgery, chemotherapy and radiotherapy. However, these methods were less successful and had major side effects. In order to improve the efficiency of cancer treatment, we focus on the development of multifunctional polymeric micelles for drug delivery, gene therapy and diagnostic imaging application. The developed polymeric micelles were composed of a hydrophobic stearic acid (SA) core and a positively charged polyethylenimine (PEI) outer shell which was modified by polyethylene glycol (PEG). The hydrophobic core served as a reservoir for superparamagnetic iron oxide nanoparticles (SPIONs) which is a magnetic resonance imaging (MRI) contrast agent with remarkably high T2 relaxivity and sensitivity. Of the hydrophilic shell, the cationic polymer PEI was used for non-viral transfection and PEG was used for prolonging blood circulation time.
In this study, we have successfully developed PEG-PEI-SA micelles confirmed by TNBS assay, nuclear magnetic resonance (NMR), transmission electron microscopy (TEM). And the DNA retardation assay demonstrated that PEG-PEI-SA micelles showed good DNA binding efficiency. The encapsulation was performed by addition of SPIONs in toluene to PEG-PEI-SA micelles solution, followed by sonication at 5 W for 1 min at 4℃. Dynamic light scattering (DLS) measurement revealed ~200nm particles (PDI = 0.2) were formed, while TEM analysis demonstrated that clusters of SPIONs were encapsulated in the hydrophobic core. And the encapsulation efficiency was about 60% which was analyzed by atomic absorption spectrometry (AAS). MRI scanning of the samples revealed that the SPIONs-loaded micelles had higher T2 relaxivity than Resovist®. In addition, in vivo study showed that the liver, kidney and prostate turned dark on T2 weighted images after tail vein injection. These results indicated that the SPIONs-loaded micelles can serve as an efficient image-guided drug and gene delivery system.
Subjects
polymeric micelles
magnetic resonance imaging (MRI)
superparamagnetic iron oxide nanoparticles (SPIONs)
gene therapy
polyethylenimine (PEI)
polyethylene glycol (PEG)
T2 relaxivity
SDGs
Type
thesis
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