Differential effects of small size gold nanoparticles on radiation and ultrasound-induce cell death

2019 Fiscal Year Research-status Report

• Project/Area Number: 19K17263
• Research Institution: University of Toyama
• Principal Investigator: ジャベド パラス 富山大学, 医学部, 研究員 (00838980)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: Gold nanoparticles / Radiation / Apoptosis

Outline of Annual Research Achievements

The objective of this study is to identify the role of various sizes of Gold nanoparticles (Au-NPs) in combination with different physical modalities. The activity of different sized Au-NPs with helium-based CAP (He-CAP) was analyzed, and the underlying mechanism was investigated. Treating cells with only small Au-NPs (2 nM) significantly enhanced He-CAP-induced apoptosis, while 40 nm and 100 nm Au-NPs failed to enhance cell death. Mechanistically, only small Au-NPs can enhance He-CAP induced apoptosis due to the decrease of intracellular GSH levels that leads to excessive generation of intracellular ROS. He-CAP markedly induced ROS generation in an aqueous medium; however, treatment with He-CAP alone did not induce intracellular ROS formation. In contrast, the combined treatment significantly enhanced the intracellular formation of superoxide and hydroxyl radical . ROS mediated damage to intracellular components and cell surface death receptor activation initiate apoptotic cell death either by intrinsic or extrinsic apoptotic pathways. These findings highlight the importance of determining the Au-NPs size-dependent effects with CAP on various cancer cells.
In addition, the effects of small size of Au-NPs with x-irradiation (x-ray) and Ultrasound (US) was investigated. Au-NPs have the ability to protect the x-ray induced apoptosis however; it enhanced the US induced cell death.

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

Only small size Au-NPs are capable to enhance He-CAP induced apoptosis via ROS formation due to the abolishment of intracellular GSH which ultimately enhance both extrinsic and intrinsic pathway of apoptosis. Research is progressing smoothly, in line with the purpose of research.

Strategy for Future Research Activity

In continuation of last year research, the effects of different sizes of Au-NPs were further observed in combination with Radiation and other physical modalities on various cell lines i-e: Human Lymphoma U937 cells, MOLt-4 cells, Human Cervical cancer HeLa and HCT-116. Next, the involvement of apoptotic pathways will be investigated by using specific dyes and inhibitors. The expression of specific markers associated with cell death and apoptosis will be examined by western blot analysis. The results will be summarized and published as a research paper.

Causes of Carryover

I change the purchase timmimg of various sizes of gold nanoparticles. For the mechanism of gold nanoparticles induced cell death, it is used as planned.