Impacts of designed vanillic acid-polymer-magnetic iron oxide nanocomposite on breast cancer cells

Abstract

The engineered nano-vehicle was constructed using magnetic iron oxide nanoparticles (MIONs) and chitosan (CTS) to stabilize anticancer agent vanillic acid (VNA) which was loaded on CTS-coated MIONs nanocarrier, and more importantly, to achieve sustained VNA release and subsequent proper anticancer activity. The new thermally stable VNA-CTS- MIONs nanocomposite was spherical with a middle diameter of 6 nm and had a high drug loading of about 11.8 %. The MIONs and resulting nanocomposite were composed of pure magnetite and therefore, were superparamagnetic with saturation magnetizations of 53.3 and 45.7 emu.g^-1, respectively. The release profiles of VNA from VNA-CTS-MIONs nanocomposite in different pH values were sustained and showed controlled pH-responsive delivery of the loaded VNA with 89 % and 74 % percentage release within 2354 and 4046 min at pH 5 and 7.4, respectively, as well as were in accordance with the pseudo-second-order model. The VNA-CTS-MIONs nanocomposite treatment at diverse concentrations remarkably decreased the viability and promoted ROS accumulation and apoptosis in the MDA-MB-231 breast cancer cells. Hence, it can be a propitious candidate for the management of breast cancer in the future.

Keywords: Anticancer nano-delivery; Breast cancer; Chitosan; Nanocomposite; Vanillic acid.

Fig. 1

Process description of MIONs, CTS-MIONs, and VNA-CTS-MIONs nanocomposite production.

Fig. 2

XRD spectra of MIONs (A), VNA-CTS-MIONs nanocomposite (B), and VNA (C).

Fig. 3

FTIR spectra of MIONs (A), CTS-MIONs (B), VNA-CTS-MIONs nanocomposite (C), and VNA (D).

Fig. 4

Scheme illustrating of the interaction amid MIONs, CTS, and VNA in the VNA-CTS-MIONs.

Fig. 5

TGA/DTG curves of VNA (A), MIONs (B), and VNA-CTS-MIONs (C).

Fig. 6

Magnetization curves of MIONs (A) and VNA-CTS-MIONs nanocomposite (B) measured at room temperature. The inset shows the magnetic behaviour in low magnetic fields.

Fig. 7

TEM images for MIONs (A) and VNA-CTS-MIONs (B), and particle size dispersal of MIONs (C) and VNA-CTS-MIONs (D).

Fig. 8

Release curves of a physical mixture of VNA with CTS-MIONs at pH 7.4 and pH 5 (A) and release curves of VNA from VNA-CTS-MIONs at pH 7.4 and pH 5 (B).

Fig. 9

Suiting of the data for VNA release from VNA-CTS-MIONs in diverse solutions to the first-order, pseudo-second order kinetics and parabolic diffusion model for pH 7.4 (A–C) and pH 5 (D–F).

Fig. 10

Effect of VNA-CTS-MIONs nanocomposite on the MDA-MB-231 cell growth. The treatment with the diverse concentrations of VNA-CTS-MIONs (2.5–15 μg) was effectively diminished the MDA-MB-231 cell viability. Values are depicted as mean ± SD of triplicate assays.

Fig. 11

Effect of VNA-CTS-MIONs nanocomposite on the ROS accumulation in the MDA-MB-231 cells. The VNA-CTS-MIONs nanocomposite and DOX treatment remarkably boosted the ROS buildup in the MDA-MB-231 cells.

Fig. 12

Effect of VNA-CTS-MIONs on the apoptosis in breast cancer cells. The treatment with VNA-CTS-MIONs and DOX led to the high yellow/orange fluorescence that proves the increased occurrence of early and late apoptosis, respectively in the MDA-MB-231 cells. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)