About This Project
Gold nanoparticles (GNPs) have been investigated as radiosensitizers for cancer therapy. GNPs lack a targeting mechanism and could cause cytotoxic side effects. GNPs can be linked to antibody for target delivery into cancer cells. Cell penetration peptide (CPP) has cell translocation capacity. Our hypothesis is that CPP paired with antibody allows efficient delivery of GNPs to cancer cells to enhance radiotherapy.
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What is the context of this research?
Gold nanoparticles (GNPs) can generate heat to cause irreversible tumor cell damage when treated by radiofrequency waves and have been investigated as radiosensitizers for cancer therapy. However, GNPs lack a targeting mechanism and could cause harmful side effects by off target delivery to normal tissues. In this study, GNPs will be linked to an anti-HER2 antibody to achieve targeted breast cancer treatment. However, the antibody is usually not internalized efficiently into cells, limiting the delivery of GNPs into cancer cells. Cell penetrating peptides (CPPs) can actively translocate through the cell membrane. Pairing antibody with CPP would promote internalization and delivery of GNPs into cancer cells with high efficiency and specificity, improving the efficacy of radiation therapy.
What is the significance of this project?
Effective cancer treatment needs to target the pathological source of the disease with minimal side effects. The aim of this project is to develop an effective method for target delivery of antibody-GNPs to sensitize cancer cells to radiotherapy and improve the efficacy of cancer treatment. CPPs can translocate through the cell membrane and deliver drugs directly to a target cell. We will evaluate whether CPP conjugated to antibody will increase the internalization of antibody and consequently the delivery of GNPs into cancer cells. The results will help us develop a feasible approach that can efficiently deliver antibody-drug to cancer cells. We will also determine the optimal radiation treatment that can augment the cytotoxicity of GNPs for more effective cancer treatment.
What are the goals of the project?
Our goal is to evaluate whether CPP increases the efficiency of target delivery of antibody-GNPs into cancer cells. An additional objective is to investigate an effective radiation treatment method to augment the cytotoxic effect of GNPs. In addition, we will determine whether more effective cell entry of GNPs mediated by CPP would result in an increased efficiency of radiation treatment. GNPs will be conjugated to a unique site on the antibody. Breast cancer cells will be treated using media, anti-HER2 antibody, GNP, antibody-GNP, and CPP-antibody-GNP. GNP entry into cancer cells will be visualized using microscope. The cells will be treated with radiation and cytotoxicity will be measured for all test groups.
Cell penetrating peptide synthesis, peptide-antibody conjugation, and GNP labeling kit are costly and critical reagents for this study. Without these items, I cannot move on with the study. The price quote for these reagents reveals the cost is much higher than what I can pay from the pocket. I have tried to look for a sponsor from industries and universities without a success. Through internet searching, I learned about crowdfunding which could support interesting research projects. This is an exciting opportunity. Please fund and support my project which may provide a novel and feasible approach for more effective cancer treatment.
We would like to start the synthesis of CPP and conjugate it to the anti-HER2 antibody by the end of December. This would take three weeks to obtain the CPP-antibody. Then CPP-antibody and antibody will be conjugated to GNP in the middle of December. By the end of December, we will treat MCF7 breast cancer cells with media, anti-HER2 antibody, GNP, antibody-GNP, and CPP-antibody-GNP. The data from imaging and cytotoxicity assay from radiotreatment will be collected.
Dec 22, 2017
Procurement of anti-HER2 antibody
Dec 29, 2017
Synthesis of cell penetrating peptide (CPP)
Dec 29, 2017
Jan 04, 2018
Conjugation of CPP to anti-HER2 antibody
Jan 24, 2018
Execution of scientific experiments
Meet the Team
Hello everyone! My name is Kevin Guo. I am currently a sophomore in Great Valley High School. I like cross country running, karate, and music in my spare time. At school, I have taken AP Biology and am currently taking AP Chemistry. These courses have prepared me to engage in scientific research in biomedical sciences. Over the past few years, I participated and won several awards in Chester County and DVSF Science Fairs. Some projects that I have undertaken include evaluating the cytotoxic effects of artificial food dyes using Daphnea Magna as a model and studying the cytotoxic effects of antibody-gold nanoparticle complex on breast cancer cells over expressing HER2. These science fair projects have inspired me in my passion for science.
I developed a passion for cancer research when I was a member of Junior National Honor Society and was involved with activities sponsored by Breast Cancer Awareness. During my involvement there, I heard so many devastating stories about patients who not only suffered from the malignancy of cancer but also left family and friends with unrelenting sorrow when the patients lost the battle. I have also had several people in my life losing their loved ones to cancer. My grandmother is currently battling with late stage lung cancer and suffers from side effects of chemotherapy. These stories made me sad and have motivated me to take on cancer research projects to make a difference and help patients to stand up to cancer.
I am launching a campaign to cover expensive reagents much needed for the project aimed to improve the efficiency of cancer radiation therapy with reduced side effects. Your contribution will make an impact. Even if you don’t donate directly, you can support my project by sharing my website link through social media or email to your friends. With the support from people like you, our cause to help cancer patients will become a reality.
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Fay, F., & Scott, C. J. (2011). Antibody-targeted nanoparticles for cancer therapy. Immunotherapy, 3(3), 381-394.
Zhao, Y., Lou, D., Burkett, J., & Kohler, H. (2001). Chemical engineering of cell penetrating antibodies. Journal of immunological methods, 254(1), 137-145.
Lim, K. J., Sung, B. H., Shin, J. R., Lee, Y. W., Yang, K. S., & Kim, S. C. (2013). A cancer specific cell-penetrating peptide, BR2, for the efficient delivery of an scFv into cancer cells. PloS one, 8(6), e66084.
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