title: Distinguishing folate-receptor-positive cells from folate-receptor-negative cells using a fluorescence off-on nanoprobe.
abstract: Based on the high affinity of folic acid (FA) for folate receptor (FR) that is overexpressed on the surface of many human cancer cells, we have developed a simple fluorescence nanoprobe (1) with multiple capability (fluorescence off-on response and cell-targeting ability) for imaging of FR-positive cells by covalently linking both FA and Rhodamine B (RB) to graphene oxide (GO) through disulfide bonds. The nanoprobe shows a weak fluorescence due to the electron transfer from GO to RB. However, the specific binding of FA to FR-positive cells leads to the internalization of the nanoprobe into the cells. As a result, the disulfide bonds of 1 are cleaved by intracellular glutathione, causing the release of the RB moiety from GO and thereby the generation of fluorescence. Compared to most of the reported fluorescence always-on nanoprobes for imaging FR-positive cells, the present fluorescence off-on nanoprobe can not only produce a high signal/background ratio but also avoid the false positive results often caused by nonspecific adsorption of the always-on nanoprobes on the surface of nontarget cells. Notably, the proposed off-on nanoprobe has been demonstrated to distinguish the cells with different expression levels of FR by culturing and analyzing different cell mixtures (Hela/NIH-3T3 and Hela/MCF-7 cells). Moreover, the nanoprobe is capable of discriminating FR-positive from FR-negative cells even with similar morphology. This method is simple and selective for fluorescence imaging of FR-positive cells.
authors.affiliation: Beijing National Laboratory for Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, People's Republic of China.
authors.forename: Duan
authors.initials: D
authors.lastname: Feng
authors.forename: Yanchao
authors.initials: Y
authors.lastname: Song
authors.forename: Wen
authors.initials: W
authors.lastname: Shi
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Li
authors.forename: Huimin
authors.initials: H
authors.lastname: Ma
mesh_terms: D000818:Animals; D058973:Folate Receptors, GPI-Anchored / Q000032:analysis; D058972:Folic Acid Transporters / Q000032:analysis*; D006367:HeLa Cells; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D041681:NIH 3T3 Cells; D053758:Nanoparticles / Q000737:chemistry*; D061848:Optical Imaging / Q000379:methods*
chemical_list: D058973:Folate Receptors, GPI-Anchored; D058972:Folic Acid Transporters