MANNosylation of Mesoporous Silica Nanoparticles Modifies TLR4 Localization and NF-κB Translocation in T24 Bladder Cancer Cells.
Mariam HohagenLaura SánchezAnn-Jacqueline HerbstHanspeter KähligJae Won ShinDavid BerryGiorgia Del FaveroFreddy KleitzPublished in: Advanced healthcare materials (2024)
D-mannose is widely used as non-antibiotic treatment for bacterial urinary tract infections. This application is based on a well-studied mechanism of binding to the type 1 bacterial pili and, therefore, blocking bacteria adhesion to the uroepithelial cells. To implement D-mannose into carrier systems, the mechanism of action of the sugar in the bladder environment is also relevant and requires investigation. Herein, two different MANNosylation strategies using mesoporous silica nanoparticles (MSNs) are described. The impact of different chemical linkers on bacterial adhesion and bladder cell response is studied via confocal microscopy imaging of the MSN interactions with the respective organisms. Cytotoxicity is assessed and the expression of Toll-like receptor 4 (TLR4) and caveolin-1 (CAV-1), in the presence or absence of simulated infection with bacterial lipopolysaccharide (LPS), is evaluated using the human urinary bladder cancer cell line T24. Further, localisation of the transcription factor NF-κB due to the MANNosylated materials is examined over time. The results show that MANNosylation modifies bacterial adhesion to the nanomaterials and significantly affects TLR4, caveolin-1, and NF-κB in bladder cells. These elements are essential components of the inflammatory cascade/pathogens response during urinary tract infections. These findings demonstrate that MANNosylation is a versatile tool to design hybrid nanocarriers for targeted biomedical applications.
Keyphrases
- toll like receptor
- nuclear factor
- inflammatory response
- urinary tract infection
- lps induced
- induced apoptosis
- signaling pathway
- spinal cord injury
- immune response
- transcription factor
- oxidative stress
- cell cycle arrest
- pi k akt
- poor prognosis
- cancer therapy
- endothelial cells
- biofilm formation
- high resolution
- single cell
- stem cells
- drug delivery
- endoplasmic reticulum stress
- mass spectrometry
- escherichia coli
- cell migration
- cell proliferation
- multidrug resistant
- solid state
- drug release
- combination therapy
- candida albicans