MMP-9 responsive mesoporous silica nanoparticles for local drug delivery to NSCLC cells

Mesoporous silica nanoparticles (MSNs) offer unique features for drug delivery such as their ability to carry a wide variety of molecules as well as be functionalized by surface coating and/or external functions for controlled drug release.1 Stimuli-responsive drug release may result in a more targeted release of the drugs, and can be achieved by a change in disease specific biological environment. Specifically, MMP-9 is overexpressed during advanced stages of NSCLC, while minimally expressed in healthy tissue, contributing to poor prognosis of lung cancer patients.2, 3 In this study, we report the novel synthesis of MSNs bearing MMP-9 responsive protein caps. The pores of these particles are closed by the caps in the absence of MMP-9, whereas cargo release was observed in a stimuli-responsive manner in the presence of MMP-9 in an in vitro approach. Dose-dependent and stimuli-responsive release was also shown for the model cargo Calcein-AM, as well as for cisplatin, in two different NSCLC cell lines, as determined by cell uptake and cell death assays, respectively. Importantly, the MSNs were non-toxic up to high concentrations as shown by Annexin-V/PI double staining and flow cytometry. Notably, the MSNs which contained non-toxic doses of two chemotherapeutics resulted in increased cell death, indicating that these particles can also be used for combination treatment. This novel drug delivery system represents a promising platform for controllable site-specific drug delivery with the possibility to deliver multiple drugs, and thus provides a promising approach for new clinical applications to combat NSCLC tumor growth.