Cellular interaction of folic acid conjugated superparamagnetic iron oxide nanoparticles and its use as contrast agent for targeted magnetic imaging of tumor cells
Manoj Kumar,1 Gurpal Singh,1 Vikas Arora,2 Sujeet Mewar,3 Uma Sharma,3 NR Jagannathan,3 Sameer Sapra,2 Amit K Dinda,4 Surender Kharbanda,5 Harpal Singh1
1Center for Biomedical Engineering, Indian Institute of Technology, Hauz Khas, New Delhi-110016, India; 2Department of Chemistry, Indian Institute of Technology, Delhi Hauz Khas, New Delhi-110016, India; 3Department Of NMR, All India Institute of Medical Sciences, Ansari Nagar New Delhi-110029, India; 4Department Of Pathology, All India Institute of Medical Sciences, Ansari Nagar New Delhi-110029, India; 5Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
Abstract: The purpose of the study was to develop tumor specific, water dispersible superparamagnetic iron oxide nanoparticles (SPIONs) and evaluate their efficacy as a contrast agent in magnetic resonance imaging (MRI). We have developed SPIONs capped with citric acid/2-bromo-2-methylpropionic acid which are compact, water dispersible, biocompatible having narrow range of size dispersity (8–10 nm), and relatively high T2 relaxivity (R2 = 222L · mmol-1 · sec-l). The targeting efficacy of unconjugated and folic acid-conjugated SPIONs (FA-SPIONS) was evaluated in a folic acid receptor overexpressing and negative tumor cell lines. Folic acid receptor-positive cells incubated with FA-SPIONs showed much higher intracellular iron content without any cytotoxicity. Ultrastructurally, SPIONs were seen as clustered inside the various stages of endocytic pathways without damaging cellular organelles and possible mechanism for their entry is via receptor mediated endocytosis. In vitro MRI studies on tumor cells showed better T2-weighted images in FA-SPIONs. These findings indicate that FA-SPIONs possess high colloidal stability with excellent sensitivity of imaging and can be a useful MRI contrast agent for the detection of cancer.
Keywords: superparamagnetic iron oxide nanoparticles (SPION), cellular internalization, magnetic resonance imaging (MRI), cancer-cell targeting ligand
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