TRAIL Conjugated Silver Nanoparticle Synthesis, Characterization and Therapeutic Effects on HT-29 Colon Cancer Cells
Fatih Birtekocak1, Gulen Melike Demirbolat2, Ozge Cevik1
1Department of Biochemistry, School of Medicine, Aydin Adnan Menderes University, Aydin, Turkey.
Abstract:
Colon cancer is one of the most prominent causes of cancer-related morbidity and mortality and curable if detected in the early stages. TNF-related apoptosis-inducing ligand (TRAIL) is a therapeutic protein and has a potential anti-cancer activity that is widely used for the treatment of several cancers. In this study, we aimed to develop a silver nanoparticle system conjugated with TRAIL and coated with PEG (AgCTP NPs) to improve the therapeutic effects of colon cancer. AgCTP NPs were characterized by UV spectrum, FTIR and zetasizer. Cytotoxicity, hemolysis assay and apoptotic effects of nanoparticles were investigated using a colon cancer cell line (HT-29) in-vitro. Treatment with AgCTP NPs effectively inhibited proliferation and colony formation of HT-29 cells. The apoptotic effects of nanoparticles on HT-29 cells were determined as Bax, Bcl-2, PARP and clv-PARP protein expression levels using Western blot. Apoptotic proteins were upregulated by AgCTP NPs. In this study, we demonstrated that AgCTP NPs had an anti-cancer effect by activating cell death. Thus, we have confirmed that silver nanoparticles can be selected as a good carrier for TRAIL therapeutic proteins that can be used to treat colon cancer.
Insights
This study developed silver nanoparticles conjugated with TNF-related apoptosis-inducing ligand (TRAIL) to treat colon cancer. The novel AgCTP NPs effectively inhibited cancer cell growth and induced cell death, showing promise for colon cancer therapy.
Area of Science:
- Nanotechnology
- Oncology
- Biochemistry
Background:
- Colon cancer poses a significant global health burden, necessitating advanced therapeutic strategies.
- TNF-related apoptosis-inducing ligand (TRAIL) exhibits potent anti-cancer activity but requires effective delivery systems.
- Developing novel drug delivery systems is crucial for enhancing the efficacy of cancer treatments.
Purpose of the Study:
- To engineer silver nanoparticles (AgNPs) conjugated with TRAIL and coated with PEG (AgCTP NPs) for improved colon cancer therapy.
- To evaluate the anti-cancer efficacy of AgCTP NPs in vitro using a colon cancer cell line.
- To investigate the mechanism of action of AgCTP NPs in inducing cancer cell death.
Main Methods:
- Characterization of AgCTP NPs using UV-Vis spectroscopy, FTIR, and dynamic light scattering (Zetasizer).
- In vitro assessment of cytotoxicity and hemolysis assays on HT-29 colon cancer cells.
- Western blot analysis to determine the expression levels of apoptotic proteins (Bax, Bcl-2, PARP, cleaved PARP).
Main Results:
- AgCTP NPs demonstrated significant inhibition of HT-29 cell proliferation and colony formation.
- Treatment with AgCTP NPs effectively induced apoptosis in colon cancer cells.
- Western blot analysis revealed upregulation of pro-apoptotic proteins (Bax, cleaved PARP) and downregulation of anti-apoptotic proteins (Bcl-2) by AgCTP NPs.
Conclusions:
- AgCTP NPs exhibit significant anti-cancer effects against colon cancer cells by activating apoptotic pathways.
- Silver nanoparticles serve as an effective carrier for TRAIL, enhancing its therapeutic potential for colon cancer.
- This study validates the use of AgCTP NPs as a promising therapeutic agent for colon cancer treatment.
