Preparation and in vitro evaluation of redox-responsive silica-loaded arsenic trioxide nano-drug delivery system / 中草药

ABSTRACT

Objective: The redox-responsive drug delivery system of MSN-SS-PEG@As2O3 was constructed based on mesoporous silica nanoparticle (MSN), which was modified by both redox-sensitive disulfide bonds and non-toxic, non-immunogenic polyglycols (PEG), and loaded the arsenic trioxide (As2O3) by electrostatic adsorption and evaluated in vitro. Methods: Silica was synthesized by coprecipitation method. The redox-responsive carrier (MSN-SS-PEG) was synthesized on the basis of silica, (3-mercaptopropyl) trimethoxysilane, 2-(2-pyridyldithio) ethylamine hydrochloride and methoxy terminated PEG. The particle size and Zeta potential of MSN-SS-PEG were measured by Malvern particle size analyzer; The structure of the carrier was verified by infrared spectroscopy; The morphology and physical and chemical properties of the carrier were investigated by transmission electron microscopy (TEM) and small angle powder diffraction; The drug loading efficiency of MSN-SS-NH2@As2O3 and MSN-SS-PEG@As2O3 were investigated by inductively coupled plasma emission spectrum (ICP). The drug loading was further verified by thermogravimetry (TGA). In vitro release characteristics of the drug delivery system under different pH conditions were investigated by dialysis bag method. MTT assay was used to investigate the toxicity of carrier and delivery system to human normal hepatocytes (L02) or human hepatocarcinoma (HepG2) cells. Results: The potential of MSN, MSN-SS-NH2, MSN-SS-PEG was (-13.40 ± 0.87), (31.63 ± 0.90), (27.70 ± 5.60) mV, respectively. The final potential of modified carrier was positive. The particle size of MSN-SS-PEG was (159.60 ± 3.10) nm. The results of TEM showed that MSN, MSN-SS-NH2 and MSN-SS-PEG were all round or quasi round; The drug loading of MSN-SS-PEG@As2O3 was 4.38%, which measured by ICP; The release in vitro showed that MSN-SS-PEG@As2O3 was redox sensitive response. Compared with L02 cells, HepG2 cells were more sensitive to the toxicity of the carrier, and with the increase of the carrier concentration, the cell survival rate of MSN-SS-PEG was higher than that of MSN-SS-NH2, suggesting that PEG modification can further reduce the cytotoxicity of the carrier and improve the biocompatibility of the carrier. In addition, MTT results showed that the inhibitory effect of MSN-SS-PEG@As2O3 on HepG2 cell was significantly higher than that of other groups. Conclusion: The carrier prepared in this paper had a round and uniform particle size. The modified silica can release under the special microenvironment of the tumor and increase the accumulation of the drug in the tumor site. The delivery system has a good application in tumor therapy as a tumor micro-environment responsive carrier.