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MIL/Aptamer as a Nanosensor Capable of Resisting Nonspecific Displacement for ATP Imaging in Living Cells


MIL/Aptamer as a Nanosensor Capable of Resisting Nonspecific Displacement for ATP Imaging in Living Cells

Jun Li et al. ACS Omega.


Fluorescent probes physisorbed on nanomaterials have emerged as a kind of useful and facile sensing platform for biological important molecules. However, nonspecific displacement in the physisorption systems is a non-negligible problem for the intracellular analysis. MIL (Materials of Institut Lavoisier), a subclass of metal-organic frameworks (MOFs), has high porosity, large surface area, and intriguing three-dimensional (3D) nanostructure with promising biological and biomedical applications such as molecular detection and drug delivery. Herein, we report MIL/aptamer-FAM as a nanosensor capable of resisting nonspecific displacement for intracellular adenosinetriphosphate (ATP) sensing and imaging. In this approach, by virtue of the remarkable quenching capability, high affinity of aptamers, and dramatic capability of resisting nonspecific displacement of 3D MIL-100, the assay and imaging of ATP in living cells were realized. Our results demonstrated that the MIL/aptamer-FAM nanosensor not only shows high selectivity for the detection of ATP in buffer but also is able to act as a "signal-on" nanosensor for specific imaging of ATP in living cells. The strategy reported here opens up a new way to develop MOF-based nanosensors for intracellular delivery and metabolite detection.

Conflict of interest statement

The authors declare no competing financial interest.


Scheme 1
Scheme 1. Schematic Illustration of MIL/Apt-F as a Nanosensor Capable of Resisting Nonspecific Displacement for ATP Imaging in Living Cells
Figure 1
Figure 1
Fluorescence emission spectra of Apt-F (10 nM) under different conditions (λex = 485 nm): (a) Apt-F in Tris-HCl buffer; (b) Apt-F and MIL-100 (0.3 mg/mL); (c) Apt-F, MIL-100, and ATP (2 mM). Inset: photographs of the corresponding luminescence.
Figure 2
Figure 2
(A) Fluorescence emission spectra of the MIL/Apt-F nanosensor (λex = 485 nm) activated by ATP with different concentrations (0.05, 0.1, 0.2, 0.3, 0.4, 0.5, 1.0, 2.0, 4.0, 8.0 mM). (B) Relative fluorescence enhancement (F/F0) of MIL/Apt-F toward different concentrations of ATP. Inset: the linear relationship between F/F0 and ATP concentration. (C) Fluorescence restoration of MIL/Apt-F by ATP as a function of time. (D) Relative fluorescence responses of the MIL/Apt-F nanosensor to 0.5 mM ATP, 1 mM AMP, CTP, GTP, or ADP, respectively. All the experiments were carried out in Tris-HCl buffer (20 mM, pH 7.2) with 0.3 mg/mL of MIL/Apt-F at room temperature, where F0 and F are the fluorescence intensities of MIL/Apt-F at 520 nm before and after treatment with ATP, respectively. Error bars were obtained from three parallel experiments.
Figure 3
Figure 3
Relative fluorescence responses of the MIL/Apt-F nanosensor to (A) different concentrations of BSA and (C) 15 μM HSA, 1 μM thrombin, 1 μM lysozyme, and cell lysis solution, respectively. (B) Fluorescence emission spectra of Apt-F (10 nM, λex = 485 nm) and Cu(H2dtoa)/Apt-F (0.2 mg/mL) in the presence of different concentrations of BSA. MIL/Apt-F (0.3 mg/mL) is employed for all the detection in Tris-HCl buffer (20 mM, pH 7.2) at room temperature.
Figure 4
Figure 4
Confocal microscopy fluorescence images (up) and the overlay of fluorescence and bright-field images (down) of HeLa cells after incubation with the MIL/Apt-F nanosensor (0.3 mg/mL) (A) and pretreated with Ca2+ (5 mM) (B) or with sodium azide (10 mM) (C) and then incubated with MIL/Apt-F. Scale bar: 50 μm.

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