PuSH - Publication Server of Helmholtz Zentrum München

van Rijt, S.H. ; Bölükbas, D.A.* ; Argyo, C.* ; Datz, S.* ; Lindner, M. ; Eickelberg, O. ; Königshoff, M. ; Bein, T.* ; Meiners, S.

Protease-mediated release of chemotherapeutics from mesoporous silica nanoparticles to ex vivo human and mouse lung tumors.

ACS Nano 9, 2377-2389 (2015)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
Nanoparticles allow for controlled and targeted drug delivery to diseased tissues and therefore bypass systemic side effects. Spatiotemporal control of drug release can be achieved by nanocarriers that respond to elevated levels of disease-specific enzymes. For example, matrix metalloproteinase 9 (MMP9) is overexpressed in tumors, is known to enhance the metastatic potency of malignant cells, and has been associated with poor prognosis of lung cancer. Here, we report the synthesis of mesoporous silica nanoparticles (MSNs) tightly capped by avidin molecules via MMP9 sequence-specific linkers to allow for site-selective drug delivery in high-expressing MMP9 tumor areas. We provide proof-of-concept evidence for successful MMP9-triggered drug release from MSNs in human tumor cells and in mouse and human lung tumors using the novel technology of ex vivo 3D lung tissue cultures. This technique allows for translational testing of drug delivery strategies in diseased mouse and human tissue. Using this method we show MMP9-mediated release of cisplatin, which induced apoptotic cell death only in lung tumor regions of Kras mutant mice, without causing toxicity in tumor-free areas or in healthy mice. The MMP9-responsive nanoparticles also allowed for effective combinatorial drug delivery of cisplatin and proteasome inhibitor bortezomib, which had a synergistic effect on the (therapeutic) efficiency. Importantly, we demonstrate the feasibility of MMP9-controlled drug release in human lung tumors.
Altmetric
Additional Metrics?
[➜Log in]
Edit extra informations Login
Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Bortezomib ; Cisplatin ; Combination Treatment ; Controlled Drug Delivery ; Ex Vivo 3d Lung Tissue Cultures ; Lung Cancer ; Matrix Metalloproteinase-9 ; Mesoporous Silica Nanoparticles ; Nanomedicine; Drug-delivery; Matrix Metalloproteinases; Poly(ethylene Glycol); Cancer Progression; In-vivo; Mmp-9; Adenocarcinoma; Bortezomib; Therapy; System
ISSN (print) / ISBN 1936-0851
e-ISSN 1936-086X
Journal ACS Nano
Quellenangaben Volume: 9, Issue: 3, Pages: 2377-2389 Article Number: , Supplement: ,
Publisher American Chemical Society (ACS)
Publishing Place Washington
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Lung Health and Immunity (LHI)
Institute of Lung Biology (LHI)
German Center for Lung Research (DZL)