Full text

Turn on search term navigation

© 2024. This work is published under https://creativecommons.org/licenses/by/4.0/ (the "License"). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Mesoporous silica nanoparticles (MSNs) have emerged as promising drug carriers that can facilitate targeted anticancer drug delivery, but efficiency studies relying on active targeting mechanisms remain elusive. This study implements in vitro 3D cocultures, so‐called microtissues, to model a physiologically relevant tumor microenvironment (TME) to examine the impact of surface‐modified MSNs without targeting ligands on the internalization, cargo delivery, and cargo release in tumor cells and cancer‐associated fibroblasts. Among these, acetylated MSNs most effectively localized in tumor cells in a 3D setting containing collagen, while other MSNs did so to a lesser degree, most likely due to remaining trapped in the extracellular matrix of the TME. Confocal imaging of hydrophobic model drug‐loaded MSNs demonstrated effective cargo release predominantly in tumor cells, both in 2D and 3D cocultures. MSN‐mediated delivery of an anticancer drug in the microtissues exhibited a significant reduction in tumor organoid size and enhanced the tumor‐specific cytotoxic effects of a γ‐secretase inhibitor, compared to the highly hydrophobic drug in free form. This inherent targeting potential suggests reduced off‐target effects and increased drug efficacy, showcasing the promise of surface modification of MSNs as a means of direct cell‐specific targeting and delivery for precise and successful targeted drug delivery.

Details

Title
Surface Modification of Mesoporous Silica Nanoparticles as a Means to Introduce Inherent Cancer‐Targeting Ability in a 3D Tumor Microenvironment
Author
Prabhakar, Neeraj 1 ; Långbacka, Erica 2 ; Özliseli, Ezgi 3 ; Mattsson, Jesse 4 ; Mahran, Alaa 5 ; Suleymanova, Ilida 6 ; Sahlgren, Cecilia 7   VIAFID ORCID Logo  ; Rosenholm, Jessica M. 3   VIAFID ORCID Logo  ; Åkerfelt, Malin 8   VIAFID ORCID Logo  ; Nees, Matthias 9   VIAFID ORCID Logo 

 Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Åbo Akademi University, Turku, Finland, Centre for Structural Systems Biology (CSSB), c/o DESY, Hamburg, Germany, Department of Physics, University of Hamburg, Hamburg, Germany 
 Biosciences, Faculty of Science and Engineering, Åbo Akademi University, Turku, Finland, Institute of Biomedicine and FICAN West Cancer Centre, University of Turku, Turku, Finland, InFLAMES Research Flagship Center, Åbo Akademi University, Turku, Finland, Turku Bioscience Centre, Åbo Akademi University and University of Turku, Turku, Finland 
 Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Åbo Akademi University, Turku, Finland 
 Institute of Biomedicine and FICAN West Cancer Centre, University of Turku, Turku, Finland 
 Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Åbo Akademi University, Turku, Finland, Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Assiut, Egypt 
 Faculty of Biological and Environmental Sciences, Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, Finland 
 Biosciences, Faculty of Science and Engineering, Åbo Akademi University, Turku, Finland, InFLAMES Research Flagship Center, Åbo Akademi University, Turku, Finland, Turku Bioscience Centre, Åbo Akademi University and University of Turku, Turku, Finland, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands, Institute for Complex Molecular Systems (ICMS), Eindhoven University of Technology, Eindhoven, The Netherlands 
 Biosciences, Faculty of Science and Engineering, Åbo Akademi University, Turku, Finland, Institute of Biomedicine and FICAN West Cancer Centre, University of Turku, Turku, Finland 
 Institute of Biomedicine and FICAN West Cancer Centre, University of Turku, Turku, Finland, Department of Biochemistry and Molecular Biology, Medical University of Lublin, Lublin, Poland 
Section
Research Article
Publication year
2024
Publication date
Sep 1, 2024
Publisher
John Wiley & Sons, Inc.
e-ISSN
26884046
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3115310339
Copyright
© 2024. This work is published under https://creativecommons.org/licenses/by/4.0/ (the "License"). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.