Investigating the toxicity of ATA nanoparticles in vitro and cardioprotective effects of ATA on DOX-induced cardiotoxicity in zebrafish

• Main Author: Lee, Eden Hui Ling
• Other Authors: Luo Qian Kathy
• Format: Final Year Project
• Language: English
• Published: 2015
• Subjects: DRNTU::Engineering::Bioengineering
• Online Access: http://hdl.handle.net/10356/65228
• Institution: Nanyang Technological University

A novel compound acetyltanshinone (ATA) has been discovered to have a prominent growth inhibition effect on breast cancer cells and may be potentially used as a chemotherapeutic drug. However, its property of low aqueous solubility and bioavailability poses a limitation on its drug efficacy. Therefore, nanoparticle drug loading, a method that is able to increase the drug’s bioavailability, was performed. The key objective of this final year project was to investigate the in vitro and in vivo effects of ATA nanoparticles. Based on the MTT assay, the ATA nanoparticles were found to have comparable drug efficacy as ATA in free form where the cell inhibition rate on cancer cells were in the range of 80-90% after 72 hours of treatment. Toxicity screening of free ATA and ATA nanoparticles in the zebrafish model was also carried out and the ATA nanoparticles were found to reduce the toxic effects of free ATA. Higher concentrations of free ATA at 20 μM and 40 μM were found to cause developmental malformations and mortality in zebrafish. A further study on whether ATA possessed cardioprotective effects against doxorubicin (DOX)-induced cardiac toxicity was carried out. Safe concentrations of free ATA were used to treat zebrafish embryos together with the usage of 50 μM of DOX. The results revealed the use of 5 μM and 10 μM was able to alleviate the DOX-induced cardiac toxicity as shown from lower incidences of cardiac abnormalities and higher heart rates compared to the group treated with solely DOX.