Synthesis and grafting of folate–PEG–PAMAM conjugates onto quantum dots for selective targeting of folate-receptor-positive tumor cells

We report the design and synthesis of folate–poly(ethylene glycol)–polyamidoamine (FPP)-functionalized CdSe/ZnS quantum dots (QDs), in which the QD plays a key role in imaging, whereas the folate–poly(ethylene glycol) (PEG) conjugates of the polyamidoamine (PAMAM) dendrimer serve as a system targeted to folate receptors in tumor cells. Dendrimer ligands such as folate–PEG grafted PAMAM of generation 3.5 are found to encapsulate and solubilize luminescent QDs through direct ligand-exchange reactions. Because of membrane expression of FA receptors in tumor cells, this class of ligand-exchanged QDs is able to target tumor cells. We have evaluated FPP-coated QDs and QDs without folate in HeLa cells and shown that cellular uptake of FPP-coated QDs is more significant than that non folate QDs in vivo imaging experiment. In particular, QDs coated with FPP are initially bound to tumor cell surfaces, followed by slow endosomal escape and release into the tumor cells. These insights are important for the design and development of nanoparticle agents for optical detection of tumor cells and bio-imaging.

Graphical abstractSpecific binding of the FPP-coated QDs to the surface of HeLa cells by membrane expression of FA-receptors in tumor cells.Figure optionsDownload full-size imageDownload high-quality image (60 K)Download as PowerPoint slide