Preparation of Targeting Nanodiamond-metaminopterone Drug System and Its Interaction with MCF-7 Cells †

doi:10.7503/cjcu20190247

Abstract

Abstract:

We fabricated a targeted nanodiamond drug system(NPF/G/M) through physical adsorption of methotrexate(MTX) using carboxylated nanodiamonds(ND-COOH) modified with polyethylene glycol diamine(H₂N-PEG-NH₂), folic acid(FA) and glycidol(GLY) as carriers. The preparation of NPF/G/M was verified by morphological observation, energy dispersive spectroscopy(EDS) of the elemental analysis, zeta potential and particle size. The results showed that NPF/G/M can be effectively released in the tumor site, which is three times than in the physiological environment(pH=7.4). Relying on the high affinity between folate and folate receptors, NPF/G/M was uptaken by tumor cells through energy, temperature, clathrin, caveolin-dependent and folate receptor-mediated endocytosis. Interestingly, toxicity tests showed that NPF/G/M can slowly release the drug into the cells and induce cell apoptosis. The above results indicate that NPF/G/M can be used as a good drug delivery system, which will provide a theoretical reference for clinical application in breast cancer.

Key words: Nanodiamond, Polyethylene glycol diamine, Folic acid, Glycidol, Methotrexate, Targeted nanodrug

CLC Number:

O631
O611.4

TrendMD:

LI Lin, XU Xinru, LI Yingqi, ZHANG Caifeng. Preparation of Targeting Nanodiamond-metaminopterone Drug System and Its Interaction with MCF-7 Cells ^†[J]. Chem. J. Chinese Universities, 2019, 40(9): 1998.

Figures/Tables 10

Fig.1 Structures of FA-NHS(A), GLY(B) and MTX(C)

Fig.2 TEM images of ND(A), NPF/G(B) and NPF/G/M(C)

Fig.3 EDS spectra of ND(A), NPF/G(B) and NPF/G/M(C) Inset: SEM images of corresponding nanomaterials.

Nanoparticles	Mass fraction of major element(%)
Nanoparticles	C	N	O
ND	97.01	0	2.99
NPF/G	81.90	7.64	10.47
NPF/G/M	75.38	8.56	16.07

Fig.4 Particle size(A) and Zeta potential(B) of various nanomaterials

Fig.5 Release curves of ND-PEG-FA/GLY/MTX nanomedicine at pH=5.5(a) and 7.4(b)

Fig.6 Effect of uptake quality of ND-PEG-FA/GLY/MTX by MCF-7 cells (A) The effect of different concentrations of free FA on the amount of ND-PEG-FA/GLY/MTX uptaken by MCF-7 cellsby flow cytometry; (B) the mechanism of ND-PEG-FA/GLY/MTX nanomedicine uptaken by MCF-7 cells; (C) dynamics of the nanomedicine ND-PEG-FA/GLY/MTX uptaken by MCF-7 cells.

Fig.7 Microscopy images of MCF-7 cells incubated with different nanoparticles for 48 h(A1—A4) and 72 h(B1—B4) (A1, B1) Control; (A2, B2) NPF/G;(A3, B3) NPF/G/M; (A4, B4) MTX.

Fig.8 Effects of various nanomaterials on MCF-7 cells viability by MTT assay with different time

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