RT Journal Article
SR Electronic
T1 MMP-9 responsive mesoporous silica nanoparticles for local drug delivery to NSCLC cells
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 3289
VO 44
IS Suppl 58
A1 Deniz Ali Bölükbas
A1 Christian Argyo
A1 Oliver Eickelberg
A1 Thomas Bein
A1 Silke Meiners
A1 Sabine H. Van Rijt
YR 2014
UL http://erj.ersjournals.com/content/44/Suppl_58/3289.abstract
AB 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, 3In 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.