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. 2017 Feb 22;3(1):8.
doi: 10.3390/gels3010008.

Carboxymethyl Cellulose-Grafted Mesoporous Silica Hybrid Nanogels for Enhanced Cellular Uptake and Release of Curcumin

Neha Tiwari  1   2 , Laxman Nawale  3 , Dhiman Sarkar  4   5 , Manohar V Badiger  6   7
Affiliations

Carboxymethyl Cellulose-Grafted Mesoporous Silica Hybrid Nanogels for Enhanced Cellular Uptake and Release of Curcumin

Neha Tiwari et al. Gels. .

Abstract

Mesoporous silica nanoparticles (MSNs) with ordered pore structure have been synthesized and used as carriers for the anticancer drug curcumin. MSNs were functionalized with amine groups and further attached with carboxymethyl cellulose (CMC) using 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC) coupling chemistry, which increased the hydrophilicity and biocompatibility of MSNs. The functionalized MSNs (MSN-NH₂ and MSN-CMC) were characterized using Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), Dynamic Light Scattering (DLS), N₂ adsorption, X-Ray Diffraction (XRD), Thermo Gravimetric Analysis (TGA) and Fourier Transform Infrared Spectroscopy (FT-IR). The in vitro release of curcumin from the ⁻NH₂ and CMC functionalized MSNs (MSN-cur-NH₂ and MSN-cur-CMC) was performed in 0.5% aqueous solution of sodium lauryl sulphate (SLS). The effect of CMC functionalization of MSNs towards cellular uptake was studied in the human breast cancer cell line MDA-MB-231 and was compared with that of MSN-NH₂ and free curcumin (cur). Both MSN-NH₂ and MSN-CMC showed good biocompatibility with the breast cancer cell line. The MTT assay study revealed that curcumin-loaded MSN-cur-CMC showed better uptake as compared to curcumin-loaded MSN-cur-NH₂. Free curcumin was used as a control and was shown to have much less internalization as compared to the curcumin-loaded functionalized MSNs due to poor bioavailability. Fluorescence microscopy was used to localize the fluorescent drug curcumin inside the cells. The work demonstrates that CMC-functionalized MSNs can be used as potential carriers for loading and release of hydrophobic drugs that otherwise cannot be used effectively in their free form for cancer therapy.

Keywords: carboxymethyl cellulose; curcumin; drug delivery; mesoporous silica nanoparticles.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Scheme 1
Scheme 1
Synthesis of carboxymethyl cellulose (CMC)-grafted mesoporous silica nanoparticles (MSNs).
Figure 1
Figure 1
Transmission electron microscopy (TEM) images of (a) MSN; (b) MSN-NH2 and (c) MSN-CMC.
Figure 2
Figure 2
(a) Particle size distribution of MSN and functionalized MSNs obtained by DLS experiments and (b) nitrogen adsorption-desorption isotherms of MSN, MSN-NH2 and MSN-cur-CMC nanoparticles.
Figure 3
Figure 3
(a) X-Ray Diffraction (XRD) patterns of MSN and MSN-NH2 and (b) Thermogravimetric Analysis (TGA) curves of MSN, MSN-NH2 and MSN-CMC.
Figure 4
Figure 4
Fourirer Transform Infrared Spectroscopy (FT-IR) Spectra of MSN, MSN-NH2 and MSN-CMC.
Scheme 2
Scheme 2
Synthesis of curcumin-loaded carboxymethyl cellulose grafted MSN.
Figure 5
Figure 5
In vitro cumulative release (%) of curcumin from MSN-cur-NH2 and MSN-cur-CMC in 0.5% sodium lauryl sulphate (SLS).
Figure 6
Figure 6
(a) % Cytotoxicity of MDAMB 231 cells incubated with MSN-NH2 and MSN-CMC and (b) % Cytotoxicity of MDA-MB-231 cells incubated with free curcumin, MSN-cur-NH2 and MSN-cur-CMC keeping the amount of curcumin same in all the samples (x axis represents concentration of free curcumin and curcumin incubated in MSN-NH2 and MSN-CMC).
Figure 7
Figure 7
Intracellular uptake of –NH2 and –CMC functionalized MSNs using fluorescence microscopy. Images of MDA-MB-231 incubated with 16 µg/mL of free curcumin, MSN-cur-NH2 (GI50 = 7 µg/mL) and MSN-cur-CMC (GI50 = 1.5 µg/mL). Control refers to the non-treated MDA-MB-231 cells. Blue fluorescence is due to nucleus staining of cells with 4’,6-Diamidino-2-Phenylindole Dihydrochloride (DAPI) and green is due to fluorescence of curcumin release inside the cells effectively in MDA-MB-231 cancer cells, which is also in agreement with the MTT assay where the comparable % cytotoxicity in the cells is absent.
Figure 8
Figure 8
Apoptosis of MDA-MB-231 cells using fluorescence microscopy. Images of MDA-MB-231 incubated with 16 µg/mL of free curcumin, MSN-cur-NH2 (GI50 = 7 µg/mL) and MSN-cur-CMC (GI50 = 1.5 µg/mL). Control refers to the non-treated MDA-MB-231 cells. Blue fluorescence is due to nucleus staining of cells with DAPI and green fluorescence is due to staining of cells by annexin V-FITC.
Figure 9
Figure 9
Apoptotic ratios of free curcumin, MSN-cur-NH2 and MSN-cur-CMC in 48 h.
See this image and copyright information in PMC

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