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.
Zhao
Yili
Y
Alan G. MacDiarmid Institute of Jilin University, Changchun 130012, China.
Liu
Sen
S
Li
Yapeng
Y
Jiang
Wei
W
Chang
Yulei
Y
Pan
Si
S
Fang
Xuexun
X
Wang
Y Andrew
YA
Wang
Jingyuan
J
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D050091:Dendrimers / Q000138:chemical synthesis*; D003952:Diagnostic Imaging; D016503:Drug Delivery Systems; D005492:Folic Acid / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000175:diagnosis*; D011092:Polyethylene Glycols / Q000138:chemical synthesis*; D045663:Quantum Dots; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000187:drug effects; D012995:Solubility; D014867:Water / Q000737:chemistry
D000970:Antineoplastic Agents; D050091:Dendrimers; C522249:PEG-PAMAM; D011956:Receptors, Cell Surface; D014867:Water; D011092:Polyethylene Glycols; D005492:Folic Acid