Two-dimensional (2D) materials have attracted tremendous interest as fluorescence quenchers of dye-labeled biomolecules for application in biosensing. Metal-organic framework (MOF) nanosheets, as a new type of 2D material, have rarely been studied as bioanalytical platforms. Herein, we synthesize a series of ultrathin lanthanide-based MOF (MOF-Ln) nanosheets as a dye-labeled aptamer platform. The fluorescence quenching or recovery on the MOF-Ln nanosheets is determined by the charge properties (positive or negative) of the labeled fluorophores. The negatively charged fluorophores experience a fluorescence 'turn-down followed by turn-down' process, whereas the positively charged fluorophores experience a fluorescence 'turn-down followed by turn-up' process. The interesting fluorescence quenching properties of the MOF-Ln nanosheets make them an excellent two-color sensing platform for the intracellular detection of biomolecules. NPG Asia Materials (2017) 9, e354; doi:10.1038/am.2017.7; published online 10 March 2017 INTRODUCTION Two-dimensional (2D) nanomaterials have been attracting extensive research interest due to their unique physical and chemical properties, as well as their potential scientific and technological applications in the fields of gas storage, sensing, electronics, energy conversion and storage, and electrocatalysis. 1 In the area of biomedical applications, 2D nanosheets with an extremely high surface area, such as graphene and its derivative graphene oxide, have been successfully used for biomedical imaging, drug delivery and cancer therapy. 2,3 Other emerging nanosheets (for example, MoS 2 , WS 2 and MnO 2 ) with a good fluorescence-quenching ability also exhibit selective adsorption affinity toward single-stranded DNA (ssDNA) versus double-stranded DNA (dsDNA). [4][5][6][7] These results have inspired studies to exploit the potential biological applications of novel 2D nanosheets. Very recently, 2D metal-organic framework (MOF) thin films or nanosheets have been successfully synthesized and exfoliated by several groups. [8][9][10] Their potential biological applications remain to be explored.MOFs are a fascinating class of functional materials that have been extensively studied for applications in gas storage, 11 catalysis, 12 separation 13 and sensing. 14 MOFs are certainly very promising for fabricating multifunctional luminescent sensors, because both the metal and the ligand units can provide platforms for generating luminescence and some guest molecules loaded on the MOFs can also emit or induce luminescence. 14 A variety of MOFs have been already