Dendrimer‐Functionalized Iron Oxide Nanoparticles for Specific Targeting and Imaging of Cancer Cells

Abstract

We demonstrated a unique approach that combines a layer‐by‐layer (LbL) self‐assembly method with dendrimer chemistry to functionalize Fe3O4 nanoparticles (NPs) for specific targeting and imaging of cancer cells. In this approach, positively charged Fe3O4 NPs (8.4 nm in diameter) synthesized by controlled co‐precipitation of FeII and FeIII ions were modified with a bilayer composed of polystyrene sulfonate sodium salt and folic acid (FA)‐ and fluorescein isothiocyanate (FI)‐functionalized poly(amidoamine) dendrimers of generation 5 (G5.NH2‐FI‐FA) through electrostatic LbL assembly, followed by an acetylation reaction to neutralize the remaining surface amine groups of G5 dendrimers. Combined flow cytometry, confocal microscopy, transmission electron microscopy, and magnetic resonance imaging studies show that Fe3O4/PSS/G5.NHAc‐FI‐FA NPs can specifically target cancer cells overexpressing FA receptors. The present approach to functionalizing Fe3O4 NPs opens a new avenue to fabricating various NPs for numerous biological sensing and therapeutic applications.

Multifunctional dendrimer/combretastatin A4 inclusion complexes enable in vitro targeted cancer therapy

“…Second, fluorescein isothiocyanate moieties were conjugated to the partially acetylated dendrimer by thiourea bonds in order to detect the intracellular uptake of the dendrimer carrier. Based on previous studies, 27,40,41 linking only five fluorescein isothiocyanate moieties onto each partially acetylated G5 dendrimer is sufficient for fluorescent detection. Third, 5 molar-equivalent folic acid molecules were conjugated to each G5.NHAc-FI dendrimer by amide bonds between the γ-carboxyl group of folic acid and the remaining primary amino group of the dendrimer, which is known to be sufficient to target cancer cells overexpressing high-affinity folic acid receptors efficiently.…”

“…The difference between KB-HFAR and KB-LFAR cells in terms of their surface expression of folic acid receptors has been quantified and demonstrated in our previous work by flow cytometry, confocal microscopy, and other imaging techniques. 40,41 Prior to exploring the targeted antitumor efficacy of the G5.NHAc-FI-FA/CA4 complexes, it was necessary to confirm the targeting specificity of the complexes to folic acid receptor-overexpressing KB cells. The fluorescein isothiocyanate moieties linked onto the G5 dendrimers enabled confocal microscopic imaging of cellular uptake and internalization of the G5.NHAc-FI-FA/CA4 complexes.…”

Original Research Article Novel Nano-Sized Iron Complex Application Using Folate Based Imaging Agent

“…Among the complexity specialists in clinical practice chelated paramagnetic salts of gadolinium (Gd) and super paramagnetic iron oxide nanoparticles (SPIONPs) are outstanding [1]. SPIONPs have been utilized as colloidal go between for attractive hyperthermia of malignancies [3].…”

“…The dendrimer goes about as a stage exchange specialist from natural to watery media and attractive NPs stabilizer [3,4,7,8,10]. In this research, we have developed anionic G2 PEGylated based dendrimers conjugated with FA.…”

Luminescent/magnetic PLGA-based hybrid nanocomposites: a smart nanocarrier system for targeted codelivery and dual-modality imaging in cancer theranostics

“…11,12 Positive and negative contrast agents are the two major types of MR contrast agents; examples of these include gadoliniumbased T 1 contrast agents 13,14 and superparamagnetic Fe 3 O 4 nanocrystal-based T 2 contrast agents. 12,15,16 Superparamagnetic Fe 3 O 4 nanoparticles have been approved for clinical diagnosis by the FDA 17 and have been the focus of various studies as negative contrast agents given their high magnetic responsiveness. 18,19 Another imaging modality is quantum dot (QD)-based fluorescence imaging, which has been extensively studied in multicolor imaging of cells, tissues, and animals.…”