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. 2014 Mar 25;9(1):146.
doi: 10.1186/1556-276X-9-146.

Carboxymethyl chitosan-folic acid-conjugated Fe3O4@SiO2 as a safe and targeting antitumor nanovehicle in vitro

Hongmei Li, Zhen Li, Jin Zhao, Baoqiang Tang, Yanhong Chen, Yikun Hu, Zhengda He, Yue Wang  1
Affiliations

Carboxymethyl chitosan-folic acid-conjugated Fe3O4@SiO2 as a safe and targeting antitumor nanovehicle in vitro

Hongmei Li et al. Nanoscale Res Lett. .

Abstract

A synthetic method to prepare a core-shell-structured Fe3O4@SiO2 as a safe nanovehicle for tumor cell targeting has been developed. Superparamagnetic iron oxide is encapsulated inside nonporous silica as the core to provide magnetic targeting. Carboxymethyl chitosan-folic acid (OCMCS-FA) synthesized through coupling folic acid (FA) with OCMCS is then covalently linked to the silica shell and renders new and improved functions because of the original biocompatible properties of OCMCS and the targeting efficacy of FA. Cellular uptake of the nanovehicle was assayed by confocal laser scanning microscope using rhodamine B (RB) as a fluorescent marker in HeLa cells. The results show that the surface modification of the core-shell silica nanovehicle with OCMCS-FA enhances the internalization of nanovehicle to HeLa cells which over-express the folate receptor. The cell viability assay demonstrated that Fe3O4@SiO2-OCMCS-FA nanovehicle has low toxicity and can be used as an eligible candidate for drug delivery system. These unique advantages make the prepared core-shell nanovehicle promising for cancer-specific targeting and therapy.

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Figures

Figure 1
Figure 1
Synthesis of Fe 3 O 4 @SiO 2 -OCMCS-FA.
Figure 2
Figure 2
Synthesis of OCMCS-FA.
Figure 3
Figure 3
1 H NMR spectra of OCMCS-FA in CF 3 COOD/D 2 O.
Figure 4
Figure 4
FTIR spectra. (a) OCMCS, (b) OCMCS-FA, (c) Fe3O4@SiO2, and (d) Fe3O4@SiO2-OCMCS-FA.
Figure 5
Figure 5
XRD spectrum. (a) Fe3O4 NPs, (b) Fe3O4@SiO2, (c) Fe3O4@SiO2-FA, and (d) Fe3O4@SiO2-OCMCS-FA.
Figure 6
Figure 6
High-resolution C 1s, O 1s, and N 1s X-ray photoelectron spectra. (a) High-resolution C 1s spectrum of Fe3O4@SiO2-OCMCS-FA, (b) high-resolution O 1s spectrum of Fe3O4@SiO2-OCMCS-FA, (c) high-resolution N 1s spectrum of Fe3O4@SiO2-OCMCS-FA, (d) high-resolution N 1s of OCMCS-FA, and (e) high-resolution N 1s spectrum of FA.
Figure 7
Figure 7
TEM images. (a) Fe3O4@SiO2 (inset: Fe3O4) and (b) Fe3O4@SiO2-OCMCS-FA (inset: SEM images of Fe3O4@SiO2-OCMCS-FA).
Figure 8
Figure 8
Magnetization curve. (a) Fe3O4(b) Fe3O4@SiO2, and (c) Fe3O4@SiO2-OCMCS-FA nanovehicle at 300 K.
Figure 9
Figure 9
Confocal laser scanning microscope images of subcellular localization. (a) RBFe3O4@SiO2 and (b) RBFe3O4@SiO2-OCMCS-FA after 2 h of incubation with HeLa cells. Nuclei were stained with DAPI.
Figure 10
Figure 10
Bio-TEM images of HeLa cells after 24 h of exposure to NPs (100 μg mL-1). (a) Control, (b) Fe3O4@SiO2-OCMCS-FA nanovehicle (inset: magnified image of the circled area) and (c, d) magnified image of Fe3O4@SiO2-OCMCS-FA nanovehicle.
Figure 11
Figure 11
Percentage of hemolysis of RBCs in the presence of Fe3O4@SiO2-OCMCS-FA at 500 μg mL-1. Water (+) and PBS (-) are used as positive and negative controls, respectively.
Figure 12
Figure 12
Cell inhibition of Fe 3 O 4 @SiO 2 -OCMCS-FA nanovehicle on HeLa and L-O2 cells.
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