Surface Modification of Mesoporous Silica Nanoparticles as a Means to Introduce Inherent Cancer‐Targeting Ability in a 3D Tumor Microenvironment

Autor: Neeraj Prabhakar, Erica Långbacka, Ezgi Özliseli, Jesse Mattsson, Alaa Mahran, Ilida Suleymanova, Cecilia Sahlgren, Jessica M. Rosenholm, Malin Åkerfelt, Matthias Nees
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Small Science, Vol 4, Iss 9, Pp n/a-n/a (2024)
Druh dokumentu: article
ISSN: 2688-4046
DOI: 10.1002/smsc.202400084
Popis: 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.
Databáze: Directory of Open Access Journals