Folate Conjugated Fluorescent Silica Nanoparticles for Labeling Neoplastic Cells

Abstract

We describe a novel technique of using fluorescent silica nanoparticles (FSNPs) to detect over-expressed folate receptors, as typical for certain malignancies (metastatic adenocarcinoma, pituitary adenoma and others). Using Stöber's method with some modification, 135 nm size FSNPs were synthesized by a hydrolysis and co-condensation reaction of tetraethylorthosilicate (TEOS), fluorescein labeled (3-aminopropyl)triethoxysilane (APTS) and a water-dispersible silane reagent, (3-trihydroxysilyl)propyl methylphosphonate (THPMP) in the presence of ammonium hydroxide catalyst. Folic acid (folate) was covalently attached to the amine modified FSNPs by a carbodiimide coupling reaction. The characterization of folate-FSNPs was performed using a variety of spectroscopic (UV-VIS and fluorescence), microscopic (transmission electron microscopy, TEM) and light scattering techniques. Folate conjugated FSNPs were then targeted to human squamous cancer cells (SCC-9). Laser scanning confocal images successfully demonstrated the labeling of SCC-9 cells and the efficacy of FSNP based detection system.

Review: Bioanalytical applications of biomolecule-functionalized nanometer-sized doped silica particles

“…Using antibodies specific to bacterial pathogens, functionalized silica nanoparticles can be utilized to detect a wide variety of bacteria, including bioterrorism agents, food borne, clinical or environmental pathogens (see Section 5.5) [146]. Fabricated multimodal nanoparticles containing gadolinium and Rubpy dye (providing for both optical and MRI detection) have also been conjugated to folic acid and then incubated with human cancer cells (A-549) [154]; and Santra et al [155] attached folic acid to fluorescein-doped silica nanoparticles to label human squamous cancer cells (SCC-9).…”

The folate receptor: What does it promise in tissue-targeted therapeutics?

“…Other current approaches tested in vitro using nanoparticle technology involve the use of folate conjugated with fluorescent silica nanoparticles [98], hydrophobic nanocrystals [99], cancer cell destruction mediated by near-infrared agents transported by carbon nanotubes containing a folate moiety [100] and lipoprotein-based nanoplataforms to reroute lipoproteins from their normal receptor to the cancer-associated FR [101].…”

Bioconjugated silica nanoparticles: Development and applications

“…For instance, folic acid, a small vitamin molecule recognized by cancer cells, was attached to dye-doped silica NPs and targeted to SCC-9 cancer cells, which overexpress folate receptors [59]. Laser scanning confocal images demonstrated that folate-fluorescent NPs were internalized via a receptor-mediated endocytosis process by the SCC-9 cells in much larger amounts compared to the normal human dermal fibroblast cells, thus confi rming the effi cacy and robustness of the detection system for human squamous cancer detection.…”