Ni-hemin metal-organic framework with highly efficient peroxidase catalytic activity: toward colorimetric cancer cell detection and targeted therapeutics

Abstract

Background: Given the great benefits of artificial enzymes, a simple approach is proposed via assembling of Ni²⁺ with hemin for synthesis of Ni-hemin metal-organic-frameworks (Ni-hemin MOFs) mimic enzyme. The formation of the Ni-hemin MOFs was verified by scanning electron microscopy, Transmission electron microscopy, X-ray powder diffraction, X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy, Energy-dispersive X-ray spectroscopy and UV-vis absorption spectroscopy. This novel nanocomposite exhibited surprising peroxidase like activity monitored by catalytic oxidation of a typical peroxidase substrate, 3,3,5,5'-tetramethylbenzidine, in the presence of H₂O₂. By using folic acid conjugated MOF nanocomposite as a recognition element, we develop a colorimetric assay for the direct detection of cancer cells.

Results: The proposed sensor presented high sensitivity and selectivity for the detection of human breast cancer cells (MCF-7) and Human Caucasian gastric adenocarcinoma. By measuring UV-vis absorbance response, a wide detection range from 50 to 10⁵ cells/mL with a detection limit as low as 10 cells/mLwas reached for MCF-7 cells. We further discuss therapeutics efficiency of Ni-hemin MOFs in the presence of H₂O₂ and ascorbic acid. Peroxidase-mimic Ni-hemin MOFs as reactive oxygen species which could damage MCF-7 cancer cells, however for normal cells (human embryonic kidney HEK 293 cells) killing effect was negligible.

Conclusions: Based on these behaviors, the developed method offers a fast, easy and cheap assay for the interest in future diagnostic and treatment application.

Keywords: H2O2; MCF-7 and Caucasian gastric adenocarcinoma cancer cells; Ni-hemin MOF; Peroxidase activity; TMB; Therapeutics efficiency.

Fig. 1

a–i SEM image and j–m TEM image of Ni-hemin MOF nanocomposite with different magnitude

Fig. 2

a XRD patterns of the Ni-hemin MOF nanocomposite, b XPS survey, c Ni 2p spectra and d Fe 2p spectra of the Ni-hemin MOF nanocomposite

Fig. 3

A EDS spectra, B TGA curve, and C FTIR of Ni-hemin MOF nanocomposite

Fig. 4

a N2 adsorption–desorption isotherm and b pore distribution

Fig. 5

A UV–vis and photographs of (a) Ni-hemin MOF solution (b) Ni-hemin MOF +TMB + H₂O₂ (c) Ni-hemin MOF +TMB + H₂O₂ +H₂SO₄, B Time-dependent UV–vis spectral changes of TMB solution with H₂O₂ catalyzed by NiO MOF, C Time-dependent absorbance changes of (a) Ni-hemin MOF solution (b) TMB + H₂O₂ (c) Ni-hemin MOF +TMB + H₂O₂ at 652 nm, and D Time-dependent absorbance changes of TMB solution with H₂O₂ at 652 nm in the presence of different concentrations of NiO MOF

Fig. 6

Steady-state kinetic analyses using the Michaelis–Menten model and Lineweaver–Burk model (insets) for Ni-hemin MOF nanocomposite by a varying the concentration of TMB with a fixed amount of H₂O₂ and b varying the concentration of H₂O₂ with a fixed amount of TMB

Fig. 7

Schematic illustration of peroxidase activity of Ni-hemin MOF for cancer cell detection

Fig. 8

a Target-directed cancer cell detection b Uu-vis absorbance changes at 450 nm upon analyzing different numbers of MCF-7 cells (1) 5 × 10¹, (2) 1 × 10², (3) 2 × 10², (4) 4 × 10², (5) 8 × 10², (6) 1.6 × 10³, (7) 3.2 × 10³ (8) 6.4 × 10³, (9) 1.3 × 10⁴, (10) 2.5 × 10⁴, (11) 5 × 10⁴, and (12) 1 × 10⁵, c the absorption intensity changes at 450 nm and photographs of the well plates (inset) with corresponding different numbers (50−1 × 10⁵) of MCF-7

Fig. 9

a Cell viability tests by MTT assay for MCF-7 cells in the presence of (a) Ni-hemin MOF with H₂O₂ (90 or 160 μM) and b Ni-hemin MOF with AA (1 or 2 mM). c HEK-293 cell viability upon treatment by Ni-hemin MOF with H₂O₂ (90 or 160 μM) and d Ni-hemin MOF with AA (1 or 2 mM)