Abstract
Gallic acid (GA), derived from land plants, possesses diverse physiological benefits, including anti-inflammatory and anticancer effects, making it valuable for biomedical applications. In this study, GA was used to modify the surface of dendritic mesoporous silica nanoparticles (DMSNs) via carbamate (DMSN-NCO-GA) or amide (DMSN-NH-GA) bonds, using a post-grafting technique. To explore GA-conjugated materials' potential in modulating cancer cell redox status, three variants of osteosarcoma cells (U2-OS) were used. These variants comprised the wild-type cells (NEO), the cells overexpressing the wild-type human Golgi anti-apoptotic protein (hGAAP), and the null mutant of hGAAP (Ct-mut), as this protein was previously demonstrated to play a role in intracellular reactive oxygen species (ROS) accumulation and cell migration. In the absence of external ROS triggers, non-modified DMSNs increased intracellular ROS in Ct-mut and NEO cells, while GA-conjugated materials, particularly DMSN-NH-GA, significantly reduced ROS levels, especially pronounced with higher GA concentrations and notably in hGAAP cells with inherently higher ROS levels. Additionaly, NH-GA conjugates were less cytotoxic, more effective in reducing cell migration, and had higher ROS buffering capacity compared to DMSN-NCO-GA materials. However, in the presence of the external stressor tert-butyl-hydroperoxide (TBHP), NCO-GA conjugates showed more efficient reduction of intracellular ROS. These findings suggest that varying chemical decoration strategies of nanomaterials, along with the accessibility of functional groups to the cellular environment, significantly influence the biological response in osteosarcoma cells. Highlighting this, GA-conjugation is a promising method for implementing antioxidant properties and inhibiting cancer cell migration, warranting further research in anticancer treatment and drug development.
| Original language | English |
|---|---|
| Pages (from-to) | 6424-6441 |
| Number of pages | 18 |
| Journal | Journal of Materials Chemistry B |
| Volume | 12 |
| Issue number | 26 |
| DOIs | |
| Publication status | Published - 3 Jul 2024 |
Bibliographical note
Publisher Copyright:© 2024 The Royal Society of Chemistry.
Funding
The authors would like to thank the University of Vienna (Austria) for the financial support. The authors thank Dr Endre Kiss for skilful technical assistance, Cornelia Schmutz and Maximilian Jobst for precious support in the implementation of the DCF and migration assays, the NMR Center and the core facility Multimodal Imaging of the Faculty of Chemistry (members of the VLSI) and Univ.-Prof. Dr Doris Marko for the provision of technical equipment of the Department of Food chemistry and Toxicology (University of Vienna).
| Funders | Funder number |
|---|---|
| Universität Wien |
Keywords
- Antineoplastic Agents/pharmacology
- Cell Line, Tumor
- Cell Proliferation/drug effects
- Cell Survival/drug effects
- Drug Screening Assays, Antitumor
- Free Radical Scavengers/chemistry
- Gallic Acid/chemistry
- Humans
- Nanoparticles/chemistry
- Osteosarcoma/drug therapy
- Particle Size
- Reactive Oxygen Species/metabolism
- Silicon Dioxide/chemistry
- Surface Properties
