A1 Refereed original research article in a scientific journal
Surface Modification of Mesoporous Silica Nanoparticles as a Means to Introduce Inherent Cancer-Targeting Ability in a 3D Tumor Microenvironment
Authors: Prabhakar, Neeraj; Långbacka, Erica; Özliseli, Ezgi; Mattsson, Jesse; Mahran, Alaa; Suleymanova, Ilida; Sahlgren, Cecilia; Rosenholm, Jessica M.; Åkerfelt, Malin; Nees, Matthias
Publisher: John Wiley & Sons
Publication year: 2024
Journal: Small Science
Journal name in source: Small Science
eISSN: 2688-4046
DOI: https://doi.org/10.1002/smsc.202400084
Web address : https://onlinelibrary.wiley.com/doi/abs/10.1002/smsc.202400084
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/457168594
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.
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Funding information in the publication:
This research was funded by the Academy of Finland (consortium project PESCADoR), grant numbers 309372-309374 (MN, CS, JMR), the Magnus Ehrnrooth Foundation (MÅ, EÖ), the Liv och Hälsa Foundation (MÅ). This research is also aligned with the strategic research profiling area “Solutions for Health” at Åbo Akademi University (funded by the Research Council of Finland, #336355). Sigrid Jusélius Foundation (EÖ, CS, JMR) Svenska Konkordiaförbundet (EL), Åbo Akademi University Foundation's Center of Excellence in Cellular Mechanostasis (CellMech) (CS), European Regional Development Fund (ERDF) REACT EU (AMBioPharma project, Centre for Additive Manufacturing for Life Science and Pharmaceutical Industry, project code A77805) (EÖ, JMR), Swedish Cultural Foundation (EÖ), and the Egyptian Government Scholarship fund (AM) are further acknowledged for financial support.
