Mesoporous silica nanoparticles functionalized with a redox-responsive biopolymer

摘要

A redox-responsive delivery system has been formulated for cancer therapy using mesoporous silica nanoparticles (MSNs). The silica surface is modified with carboxylic acid groups prior to loading with 5-fluorouracil (5-FU). Subsequently, the pores of the MSNs are sealed by reacting cystamine-modified carboxymethyl cellulose (CMC), which contains disulfide bonds, with the surface of the MSNs via carbodiimide chemistry. Because these bonds are the sites of cleavage, cells overexpressing reducing agents should be able to cleave Cystamine-modified CMC and release the encapsulated drug. Characterization of the resulting nanoparticles shows a decrease in surface area and pore volume, which suggests that the pores of MSNs has been sealed by the attachment of Cystamine-modified CMC. Transmission electron microscopy confirms these results and shows a coating of Cystamine-modified CMC on the surface of the MSNs. The release of 5-FU can be triggered in the presence of dithiothreitol (DDT), a reducing agent. The breast cancer cells (MCF-7) show the positive uptake of Redox-responsive MSNs Moreover, these nanoparticles exhibit higher cytotoxicity when the breast cancer cells are preincubated with DTT compared to the control nanoparticles or 5-FU loaded MSNs in the absence of DTT. These results show that MSNs crosslinked with Cystamine-modified CMC are redox-responsive and can be developed further for cancer therapy.